Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer

April 16, 2024 updated by: National Cancer Institute (NCI)

A Prospective, Multi-Institutional Phase II Trial Evaluating Temozolomide vs. Temozolomide and Olaparib for Advanced Pheochromocytoma and Paraganglioma

This phase II trial studies how well the addition of olaparib to the usual treatment, temozolomide, works in treating patients with neuroendocrine cancer (pheochromocytoma or paraganglioma) that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Poly (adenosine diphosphate [ADP]-ribose) polymerases (PARPs) are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving olaparib with temozolomide may shrink or stabilize the cancer in patients with pheochromocytoma or paraganglioma better than temozolomide alone.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the progression-free survival (PFS) of patients with advanced pheochromocytoma and paraganglioma (APP) receiving temozolomide (dose dense) and olaparib to that of patients receiving temozolomide (pulse dose) alone.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) of patients with APP receiving temozolomide (dose dense) and olaparib versus (vs.) temozolomide (pulse dose) alone.

II. To compare the objective response rate (ORR) associated with temozolomide (dose dense) and olaparib vs. temozolomide (pulse dose) alone in patients with APP.

III. To evaluate and compare the toxicity profile of temozolomide-based combinations (temozolomide [dose dense] and olaparib vs. temozolomide [pulse dose]) in patients with APP using Common Terminology Criteria for Adverse Events (CTCAE) and Patient-Reported Outcomes (PRO)-CTCAE.

OTHER OBJECTIVE:

I. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

EXPLORATORY OBJECTIVES:

I. To assess biochemical response: serum catecholamines and metanephrines; urine catecholamines and metanephrines.

II. To assess biomolecular markers associated with clinical outcome: germline succinyl dehydrogenase (SDH) mutations and tumor status of the repair enzyme methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive temozolomide orally (PO) once daily (QD) and olaparib PO twice daily (BID) on days 1-7. Treatment with temozolomide repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Cycles of olaparib repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with contrast or magnetic resonance imaging (MRI) throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

ARM II: Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

Patients discontinuing treatment due to reasons other than disease progression are followed every 8 weeks until disease progression, then every 6 months until 5 years after start of treatment. Patients discontinuing treatment due to disease progression are followed every 6 months for 5 years after start of treatment.

Study Type

Interventional

Enrollment (Estimated)

76

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 98508
        • Suspended
        • Anchorage Associates in Radiation Medicine
      • Anchorage, Alaska, United States, 99504
        • Suspended
        • Anchorage Radiation Therapy Center
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Breast Care and Surgery LLC
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Oncology and Hematology LLC
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Alaska Women's Cancer Care
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Anchorage Oncology Centre
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Katmai Oncology Group
      • Anchorage, Alaska, United States, 99508
        • Suspended
        • Providence Alaska Medical Center
    • California
      • Burbank, California, United States, 91505
        • Suspended
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Suspended
        • Holy Cross Hospital
      • Jacksonville, Florida, United States, 32224-9980
        • Withdrawn
        • Mayo Clinic in Florida
    • Idaho
      • Boise, Idaho, United States, 83712
        • Suspended
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, United States, 83619
        • Suspended
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Suspended
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83686
        • Suspended
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Suspended
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Bloomington, Illinois, United States, 61704
        • Recruiting
        • Illinois CancerCare-Bloomington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Canton, Illinois, United States, 61520
        • Recruiting
        • Illinois CancerCare-Canton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Carthage, Illinois, United States, 62321
        • Recruiting
        • Illinois CancerCare-Carthage
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Centralia, Illinois, United States, 62801
        • Recruiting
        • Centralia Oncology Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Chih-Yi Liao
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Dixon, Illinois, United States, 61021
        • Recruiting
        • Illinois CancerCare-Dixon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 815-285-7800
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Eureka, Illinois, United States, 61530
        • Recruiting
        • Illinois CancerCare-Eureka
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Galesburg, Illinois, United States, 61401
        • Recruiting
        • Illinois CancerCare-Galesburg
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Kewanee, Illinois, United States, 61443
        • Recruiting
        • Illinois CancerCare-Kewanee Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Macomb, Illinois, United States, 61455
        • Recruiting
        • Illinois CancerCare-Macomb
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • New Lenox, Illinois, United States, 60451
        • Recruiting
        • UC Comprehensive Cancer Center at Silver Cross
        • Contact:
        • Principal Investigator:
          • Chih-Yi Liao
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Orland Park, Illinois, United States, 60462
        • Recruiting
        • University of Chicago Medicine-Orland Park
        • Contact:
        • Principal Investigator:
          • Chih-Yi Liao
      • Ottawa, Illinois, United States, 61350
        • Recruiting
        • Illinois CancerCare-Ottawa Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Pekin, Illinois, United States, 61554
        • Recruiting
        • Illinois CancerCare-Pekin
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois CancerCare-Peoria
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peru, Illinois, United States, 61354
        • Recruiting
        • Illinois CancerCare-Peru
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Princeton, Illinois, United States, 61356
        • Recruiting
        • Illinois CancerCare-Princeton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Washington, Illinois, United States, 61571
        • Recruiting
        • Illinois CancerCare - Washington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-411-1222
        • Principal Investigator:
          • Jaydira Del Rivero
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Kimberly J. Perez
      • Newton, Massachusetts, United States, 02467
        • Suspended
        • Dana-Farber Cancer Institute - Chestnut Hill
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Brighton, Michigan, United States, 48114
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Canton, Michigan, United States, 48188
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Caro, Michigan, United States, 48723
        • Suspended
        • Caro Cancer Center
      • Chelsea, Michigan, United States, 48118
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Clarkston, Michigan, United States, 48346
      • Clarkston, Michigan, United States, 48346
      • Detroit, Michigan, United States, 48236
        • Recruiting
        • Ascension Saint John Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • East China Township, Michigan, United States, 48054
        • Recruiting
        • Great Lakes Cancer Management Specialists-Doctors Park
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Cancer and Blood Disease Treatment Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Hurley Medical Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Recruiting
        • Academic Hematology Oncology Specialists
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Recruiting
        • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Suspended
        • Michigan Breast Specialists-Grosse Pointe Woods
      • Lansing, Michigan, United States, 48912
        • Suspended
        • University of Michigan Health - Sparrow Lansing
      • Livonia, Michigan, United States, 48154
        • Suspended
        • Hope Cancer Clinic
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Macomb, Michigan, United States, 48044
        • Recruiting
        • Great Lakes Cancer Management Specialists-Macomb Medical Campus
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Macomb, Michigan, United States, 48044
        • Suspended
        • Michigan Breast Specialists-Macomb Township
      • Marlette, Michigan, United States, 48453
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of Marlette
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • 21st Century Oncology-Pontiac
        • Principal Investigator:
          • Elie G. Dib
        • Contact:
      • Pontiac, Michigan, United States, 48341
      • Pontiac, Michigan, United States, 48341
      • Pontiac, Michigan, United States, 48341
        • Suspended
        • Hope Cancer Center
      • Rochester Hills, Michigan, United States, 48309
        • Suspended
        • Great Lakes Cancer Management Specialists-Rochester Hills
      • Saginaw, Michigan, United States, 48601
        • Recruiting
        • Ascension Saint Mary's Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Saginaw, Michigan, United States, 48604
        • Recruiting
        • Oncology Hematology Associates of Saginaw Valley PC
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Sterling Heights, Michigan, United States, 48312
        • Recruiting
        • Bhadresh Nayak MD PC-Sterling Heights
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Tawas City, Michigan, United States, 48764
        • Recruiting
        • Ascension Saint Joseph Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Warren, Michigan, United States, 48093
        • Recruiting
        • Great Lakes Cancer Management Specialists-Macomb Professional Building
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Warren, Michigan, United States, 48093
        • Recruiting
        • Saint John Macomb-Oakland Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Warren, Michigan, United States, 48088
        • Suspended
        • Advanced Breast Care Center PLLC
      • Warren, Michigan, United States, 48093
        • Suspended
        • Macomb Hematology Oncology PC
      • Warren, Michigan, United States, 48093
        • Suspended
        • Michigan Breast Specialists-Warren
      • West Branch, Michigan, United States, 48661
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Suspended
        • Fairview Ridges Hospital
      • Burnsville, Minnesota, United States, 55337
        • Suspended
        • Minnesota Oncology - Burnsville
      • Cambridge, Minnesota, United States, 55008
        • Suspended
        • Cambridge Medical Center
      • Coon Rapids, Minnesota, United States, 55433
        • Suspended
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Suspended
        • Fairview Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Active, not recruiting
        • Unity Hospital
      • Maple Grove, Minnesota, United States, 55369
        • Suspended
        • Fairview Clinics and Surgery Center Maple Grove
      • Maplewood, Minnesota, United States, 55109
        • Suspended
        • Minnesota Oncology Hematology PA-Maplewood
      • Maplewood, Minnesota, United States, 55109
        • Suspended
        • Saint John's Hospital - Healtheast
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Abbott-Northwestern Hospital
        • Contact:
        • Principal Investigator:
          • Daniel M. Anderson
      • Minneapolis, Minnesota, United States, 55415
        • Suspended
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55454
        • Suspended
        • Health Partners Inc
      • Monticello, Minnesota, United States, 55362
        • Suspended
        • Monticello Cancer Center
      • New Ulm, Minnesota, United States, 56073
        • Suspended
        • New Ulm Medical Center
      • Princeton, Minnesota, United States, 55371
        • Suspended
        • Fairview Northland Medical Center
      • Robbinsdale, Minnesota, United States, 55422
        • Suspended
        • North Memorial Medical Health Center
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Mabel Ryder
      • Saint Louis Park, Minnesota, United States, 55416
        • Suspended
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, United States, 55102
        • Suspended
        • United Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Suspended
        • Regions Hospital
      • Shakopee, Minnesota, United States, 55379
        • Suspended
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Suspended
        • Lakeview Hospital
      • Waconia, Minnesota, United States, 55387
        • Suspended
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Suspended
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Suspended
        • Minnesota Oncology Hematology PA-Woodbury
      • Wyoming, Minnesota, United States, 55092
        • Suspended
        • Fairview Lakes Medical Center
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
    • Montana
      • Missoula, Montana, United States, 59802
        • Suspended
        • Saint Patrick Hospital - Community Hospital
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Nitya P. Raj
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Vineeth Sukrithan
    • Oklahoma
      • Lawton, Oklahoma, United States, 73505
        • Recruiting
        • Cancer Centers of Southwest Oklahoma Research
        • Contact:
          • Site Public Contact
          • Phone Number: 877-231-4440
        • Principal Investigator:
          • Adanma Anji Ayanambakkam Attanathi
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Adanma Anji Ayanambakkam Attanathi
    • Oregon
      • Bend, Oregon, United States, 97701
        • Suspended
        • Saint Charles Health System
      • Clackamas, Oregon, United States, 97015
        • Suspended
        • Clackamas Radiation Oncology Center
      • Clackamas, Oregon, United States, 97015
        • Recruiting
        • Providence Cancer Institute Clackamas Clinic
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Coos Bay, Oregon, United States, 97420
        • Suspended
        • Bay Area Hospital
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97239
        • Not yet recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Michael C. Heinrich
      • Redmond, Oregon, United States, 97756
        • Suspended
        • Saint Charles Health System-Redmond
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Recruiting
        • Lehigh Valley Hospital-Cedar Crest
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Bethlehem, Pennsylvania, United States, 18017
        • Recruiting
        • Lehigh Valley Hospital - Muhlenberg
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • East Stroudsburg, Pennsylvania, United States, 18301
        • Suspended
        • Pocono Medical Center
      • Hazleton, Pennsylvania, United States, 18201
        • Suspended
        • Lehigh Valley Hospital-Hazleton
    • Utah
      • Farmington, Utah, United States, 84025
        • Recruiting
        • Farmington Health Center
        • Contact:
        • Principal Investigator:
          • Heloisa P. Soares
      • Salt Lake City, Utah, United States, 84106
        • Recruiting
        • University of Utah Sugarhouse Health Center
        • Contact:
        • Principal Investigator:
          • Heloisa P. Soares
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Heloisa P. Soares
    • Washington
      • Aberdeen, Washington, United States, 98520
        • Suspended
        • Providence Regional Cancer System-Aberdeen
      • Bellingham, Washington, United States, 98225
        • Suspended
        • PeaceHealth Saint Joseph Medical Center
      • Centralia, Washington, United States, 98531
        • Suspended
        • Providence Regional Cancer System-Centralia
      • Edmonds, Washington, United States, 98026
        • Suspended
        • Swedish Cancer Institute-Edmonds
      • Everett, Washington, United States, 98201
        • Suspended
        • Providence Regional Cancer Partnership
      • Issaquah, Washington, United States, 98029
        • Suspended
        • Swedish Cancer Institute-Issaquah
      • Kennewick, Washington, United States, 99336
        • Recruiting
        • Kadlec Clinic Hematology and Oncology
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Lacey, Washington, United States, 98503
        • Suspended
        • Providence Regional Cancer System-Lacey
      • Longview, Washington, United States, 98632
        • Suspended
        • PeaceHealth Saint John Medical Center
      • Seattle, Washington, United States, 98104
        • Suspended
        • Pacific Gynecology Specialists
      • Seattle, Washington, United States, 98107
        • Suspended
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122-5711
        • Suspended
        • Swedish Medical Center-Cherry Hill
      • Seattle, Washington, United States, 98122
        • Suspended
        • Swedish Medical Center-First Hill
      • Sedro-Woolley, Washington, United States, 98284
        • Suspended
        • PeaceHealth United General Medical Center
      • Shelton, Washington, United States, 98584
        • Suspended
        • Providence Regional Cancer System-Shelton
      • Vancouver, Washington, United States, 98664
        • Recruiting
        • PeaceHealth Southwest Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Walla Walla, Washington, United States, 99362
        • Suspended
        • Providence Saint Mary Regional Cancer Center
      • Yelm, Washington, United States, 98597
        • Suspended
        • Providence Regional Cancer System-Yelm
    • Wisconsin
      • New Richmond, Wisconsin, United States, 54017
        • Suspended
        • Cancer Center of Western Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documentation of disease

    • Histologic documentation: Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma
    • Stage: Advanced (metastatic or unresectable primary) disease
    • Tumor site: Histologically-proven pheochromocytoma or paraganglioma
    • Radiographic evaluation: Radiographic evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in the 12 months prior to registration

  • Measurable disease

    • Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as >= 1 cm with CT or MRI (or >= 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung
  • Prior treatment with other somatostatin analog, chemotherapy, radiotherapy (including peptide radionuclide receptor therapy [PRRT]), or surgery must be completed >= 28 days prior to registration. Patients must have recovered from any effects of any major surgery prior to registration
  • Prior treatment with radiolabeled metaiodobenzylguanidine (MIBG) must be completed >= 12 weeks prior to registration and lifetime cumulative 131I-MIBG dose must be < 1000 MBq kg^-1 (36 mCi kg^-1)
  • Prior treatment with antibiotics must be completed >= 7 days prior to registration
  • No prior treatment with temozolomide, dacarbazine, or a poly ADP ribose polymerase (PARP) inhibitor
  • No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required

  • Contraception

    • Therapy utilized in this trial is associated with medium/high fetal risk
    • Women of childbearing potential and their partners, who are sexually active, must agree to use two highly effective forms of contraception in combination. This should be started from the time of registration and continue throughout the period of taking study treatment and for at least 1 month after last dose of study drug(s), or they must totally/truly abstain from any form of sexual intercourse
    • Male patients must use a condom during treatment and for 3 months after the last dose of study drug(s) when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. Male patients should not donate sperm throughout the period of taking study drug(s) and for 3 months following the last dose of study drug(s)
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3

  • Hemoglobin >= 10 mg/dL if prior radionuclide therapy Hemoglobin >= 8 mg/dL if no prior radionuclide therapy

    • In the absence of transfusion within the previous 24 hours. Radionuclide therapy includes PRRT or MIBG

  • Total bilirubin =< 1.5 x upper limit of normal (ULN)

    • Except in the case of Gilbert's syndrome, then total bilirubin must be =< 3.0 x ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN

  • Creatinine < 1.5 x ULN OR calculated (calc.) creatinine clearance > 50 mL/min

    • Calculated by Cockcroft-Gault equation
  • No indication of uncontrolled, potentially reversible cardiac condition(s) as determined by investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's formula-corrected QT interval [QTcF] prolongation > 500 msec, electrolyte disturbances, etc.) and no known congenital long QT syndrome
  • No extensive bilateral lung disease or pneumonitis
  • No abnormal organ or bone marrow function =< 28 days prior to registration
  • Patients with human immunodeficiency virus (HIV) positivity are allowed if CD4 count > 250 cells/uL and they have an undetectable HIV viral load within 6 months of registration
  • No active infection
  • No history of myelodysplastic syndrome (MDS) (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia
  • No known gastrointestinal condition(s) that might predispose for drug intolerability or poor drug absorption
  • No known medical condition causing an inability to swallow oral formulations of agents
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to PARP inhibitors
  • Concurrent use of combination antiretroviral therapy (ART) is not permitted
  • Chronic concomitant treatment with strong or moderate CYP3A4 inducers or inhibitors is not allowed. Patients must discontinue the agent(s) >= 21 days prior to registration; enzalutamide and/or phenobarbital must be discontinued >= 5 weeks prior to registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (temozolomide, olaparib)
Patients receive temozolomide PO QD and olaparib PO BID on days 1-7. Treatment with temozolomide repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Cycles of olaparib repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Olaparib
Given PO
Other Names:
  • Lynparza
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • PARP Inhibitor AZD2281
  • Olanib
  • Olaparix
Drug: Temozolomide
Given PO
Other Names:
  • Temodar
  • SCH 52365
  • Temodal
  • Temcad
  • Methazolastone
  • RP-46161
  • Temomedac
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Gliotem
  • Temizole
Procedure: Computed Tomography with Contrast
Undergo CT with contrast
Other Names:
  • Contrast Enhanced Computed Tomography
  • CONTRAST ENHANCED CT SCAN
  • Contrast-enhanced Computed Tomography
  • CT Scan With Contrast
  • CT with Contrast
Active Comparator: Arm II (temozolomide)
Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Temozolomide
Given PO
Other Names:
  • Temodar
  • SCH 52365
  • Temodal
  • Temcad
  • Methazolastone
  • RP-46161
  • Temomedac
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Gliotem
  • Temizole
Procedure: Computed Tomography with Contrast
Undergo CT with contrast
Other Names:
  • Contrast Enhanced Computed Tomography
  • CONTRAST ENHANCED CT SCAN
  • Contrast-enhanced Computed Tomography
  • CT Scan With Contrast
  • CT with Contrast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From randomization to the first documentation of disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) or death, assessed up to 5 years
Will be compared between treatment arms using the un-stratified log-rank test at one-sided level of 0.11 and the p-value will be used for decision making. The hazard ratio will be estimated using a Cox proportional hazards model and the 95% confidence interval for the hazard ratio will be provided. Results from a stratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced. Brookmeyer-Crowley methodology will be used to construct the 95% confidence interval for the median PFS for each treatment arm.
From randomization to the first documentation of disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) or death, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From randomization to death due to any cause, assessed up to 5 years
Patients who are alive will be censored at last follow-up. The distribution of survival time will be estimated using the method of Kaplan-Meier. OS will be compared between treatment arms using the log-rank test. OS medians, survival rates and hazard ratio will be estimated along with 95% confidence intervals.
From randomization to death due to any cause, assessed up to 5 years
Objective response
Time Frame: Up to 5 years
Will be assessed by RECIST version 1.1 criteria. Will be estimated using objective response rate where objective response rate is defined as the number of evaluable patients achieving a response (partial response or complete response per RECIST version 1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared across arms using a Chi-Square Test for Proportion. Point estimates will be generated for objective response rates within each arm along with 95% binomial confidence intervals.
Up to 5 years
Incidence of adverse events
Time Frame: Up to 5 years
Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The term toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events standard toxicity grading. Similarly, scores (0-4) and the maximum score for each Patient-Reported Outcomes-CTCAE item will be recorded for each patient.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical response
Time Frame: Up to 5 years
Levels of chromogranin A, urine and/or plasma catecholamines and metanephrines may predict response to therapy. The proportion of patients with a biochemical response of partial response or better, as determined by plasma and/or urine catecholamines and metanephrines, will be calculated, and a 95% confidence interval will be placed on this proportion. For each factor, we will calculate the mean +/- standard deviation, minimum, maximum, and quartiles; in addition, we will generate box and whisker plot.
Up to 5 years
Biomolecular markers associated with clinical outcome
Time Frame: Up to 5 years
Will analyze for methyltransferase (MGMT) methylation expression in archival tumors and correlate with the radiographic response rate in metastatic pheochromocytoma/paraganglioma. This is hypothesis generated box and whisker plot.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jaydira Del Rivero, Alliance for Clinical Trials in Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2021

Primary Completion (Estimated)

February 28, 2025

Study Completion (Estimated)

February 28, 2025

Study Registration Dates

First Submitted

May 19, 2020

First Submitted That Met QC Criteria

May 19, 2020

First Posted (Actual)

May 20, 2020

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-03379 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • A021804 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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