S1313, PEGPH20 in Treating Patients With Newly Diagnosed Metastatic Pancreatic Cancer

S1313, A Phase IB/II Randomized Study of Modified FOLFIRINOX + Pegylated Recombinant Human Hyaluronidase (PEGPH20) Versus Modified FOLFIRINOX Alone in Patients With Good Performance Status Metastatic Pancreatic Adenocarcinoma

This partially randomized phase I/II trial studies the side effects and best dose of pegylated recombinant human hyaluronidase (PEGPH20) when given together with combination chemotherapy and to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed pancreatic cancer that has spread to other places in the body. Pegylated recombinant human hyaluronidase may help chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, 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. It is not yet known whether combination chemotherapy is more effective with or without pegylated recombinant human hyaluronidase in treating pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-fluorouracil; Drug: PEGPH20

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with mFOLFIRINOX alone. (Phase II)

SECONDARY OBJECTIVES:

I. To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.

II. To assess objective tumor response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.

III. To determine the frequency, severity, and tolerability of adverse events of mFOLFIRINOX with PEGPH20.

TERTIARY OBJECTIVES:

I. To explore the correlation of maximum decrease in cancer antigen (CA) 19-9 levels and time to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response.

II. To explore the correlation of plasma hyaluronan (HA) and tumor expression of HA with overall survival, progression-free survival and response.

OUTLINE: This is a phase I, dose de-escalation study of pegylated recombinant human hyaluronidase followed by a randomized phase II study.

PHASE I: Patients receive pegylated recombinant human hyaluronidase intravenously (IV) over 10 minutes on day 1*; oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2; and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pegylated recombinant human hyaluronidase IV over 10 minutes on day 1* and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

*NOTE: Some patients also receive pegylated recombinant human hyaluronidase on day 3 or 4 of courses 1 and 2.

After completion of study treatment, patients are followed up for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Medical Center-University Campus
  • California
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Burlingame, California, United States, 94010
      • Mills - Peninsula Hospitals
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Corona, California, United States, 92879
      • City of Hope Corona
    • Costa Mesa, California, United States, 92627
      • UC Irvine Health Cancer Center-Newport
    • Davis, California, United States, 95616
      • Sutter Davis Hospital
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95816
      • Sutter General Hospital
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • Santa Cruz, California, United States, 95065
      • Palo Alto Medical Foundation-Santa Cruz
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • West Covina, California, United States, 91790
      • City of Hope West Covina
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • Smilow Cancer Hospital-Derby Care Center
    • Fairfield, Connecticut, United States, 06824
      • Smilow Cancer Hospital Care Center-Fairfield
    • Guilford, Connecticut, United States, 06437
      • Medical Oncology and Hematology Group PC-Guilford
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Center/Yale-New Haven Hospital
    • North Haven, Connecticut, United States, 06473
      • Yale-New Haven Hospital North Haven Medical Center
    • Orange, Connecticut, United States, 06477
      • Smilow Cancer Hospital-Orange Care Center
    • Torrington, Connecticut, United States, 06790
      • Charlotte Hungerford Hospital Center for Cancer Care
    • Trumbull, Connecticut, United States, 06611
      • Smilow Cancer Hospital Care Center-Trumbull
    • Waterbury, Connecticut, United States, 06708
      • Smilow Cancer Hospital-Waterbury Care Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Mountain States Tumor Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Mountain States Tumor Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Mountain States Tumor Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Center of Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Radiation Oncology of Northern Illinois
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
    • Swansea, Illinois, United States, 62226
      • Cancer Care Specialists of Illinois-Swansea
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Kansas Institute of Medicine Cancer and Blood Center
    • Lenexa, Kansas, United States, 66219
      • Minimally Invasive Surgery Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Medical Center-Goldschmidt Cancer Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology and Oncology Associates Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • Missouri Baptist Outpatient Center-Sunset Hills
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Hendersonville, North Carolina, United States, 28791
      • Hendersonville Hematology and Oncology at Pardee
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Mebane, North Carolina, United States, 27302
      • Cone Heath Cancer Center at Mebane
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Memorial Hospital
    • Wilson, North Carolina, United States, 27893
      • Southeastern Medical Oncology Center-Wilson
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Oncology and Hematology Care Southeast
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Medical Center-Edmonds
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kirkland, Washington, United States, 98034
      • Seattle Cancer Care Alliance at EvergreenHealth
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center-DHEC-Downtown
    • Spokane Valley, Washington, United States, 99216
      • Rockwood Clinic Cancer Treatment Center-Valley
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• Patients must have newly diagnosed, untreated metastatic histologically or cytologically documented pancreatic adenocarcinoma; patients must not have known history of brain metastases
• Patients must have measurable metastatic disease; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; CT scans or MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
• Patients must not have had any prior treatment with oxaliplatin or irinotecan within 3 years prior to registration; patients must not have had prior chemotherapy in metastatic setting; prior abdominal radiation therapy is not allowed
• Patients must have a Zubrod performance status of 0-1
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Total bilirubin =< institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 X IULN in the absence of liver metastases or =< 5.0 x IULN with liver metastasis
• Serum albumin >= 3 g/dL
• Serum creatinine =< ULN within 14 days prior to registration OR calculated creatinine clearance > 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration
• Patients must have international normalized ratio (INR) =< 1.2 within 14 days prior to registration; patients must not be receiving warfarin for therapeutic use, have history of cerebrovascular accident (CVA), history of transient ischemic attack (TIA) requiring intervention or treatment, pre-existing carotid artery disease requiring intervention or treatment, or current use of megestrol acetate (use within 10 days of registration)
• Patients must not be receiving chronic treatment (equivalent of prednisone > 10 mg/day) with systemic steroids or other immuno-suppressive agent
• Patients must not have liver disease such a cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Patients must not have active bleeding or a pathological condition that is associated with a high risk of bleeding
• Patients with a known history of human immunodeficiency virus (HIV) must not be on active treatment for HIV
• Patients must have no non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Patients must have tumor (paraffin block or slides) available for submission and be willing to submit tumor and blood samples
• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• Patients planning to enroll in the phase I portion of this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phase II: mFOLFIRINOX; Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Oxaliplatin; 85 mg/m^2, on Day 2, IV over 2 hours; Other Names: Eloxatin; NSC-266046; Drug: Leucovorin; 400 mg/m^2, on Day 2, IV over 2 hours; Other Names: leucovorin calcium; Drug: Irinotecan; 180 mg/m^2, on Day 2, IV over 1.5 hours; Other Names: CPT-11; NSC-616348; Drug: 5-fluorouracil; 2,400 mg/m^2, Days 2-4, IV over 46 hours; Other Names: 5-FU; Adrucil; NSC-19893
Experimental: Phase II: mFOLFIRINOX + PEGPH20; Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Oxaliplatin; 85 mg/m^2, on Day 2, IV over 2 hours; Other Names: Eloxatin; NSC-266046; Drug: Leucovorin; 400 mg/m^2, on Day 2, IV over 2 hours; Other Names: leucovorin calcium; Drug: Irinotecan; 180 mg/m^2, on Day 2, IV over 1.5 hours; Other Names: CPT-11; NSC-616348; Drug: 5-fluorouracil; 2,400 mg/m^2, Days 2-4, IV over 46 hours; Other Names: 5-FU; Adrucil; NSC-19893; Drug: PEGPH20; 3 ug/kg on Day 1, IV over 15 minutes; Other Names: Pegylated Recombinant Human Hyaluronidase
Experimental: Phase I; PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours	Drug: Oxaliplatin; 85 mg/m^2, on Day 2, IV over 2 hours; Other Names: Eloxatin; NSC-266046; Drug: Leucovorin; 400 mg/m^2, on Day 2, IV over 2 hours; Other Names: leucovorin calcium; Drug: Irinotecan; 180 mg/m^2, on Day 2, IV over 1.5 hours; Other Names: CPT-11; NSC-616348; Drug: 5-fluorouracil; 2,400 mg/m^2, Days 2-4, IV over 46 hours; Other Names: 5-FU; Adrucil; NSC-19893; Drug: PEGPH20; 3 ug/kg on Day 1, IV over 15 minutes; Other Names: Pegylated Recombinant Human Hyaluronidase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX	Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion. MTD of PEGPH20 in combination with mFOLFORINOX was evaluated by testing decreasing doses of PEGPH20 from 3mcg/kg on Day 1 and Day 3/4, to 3mcg/kg on Day 1 only and to 1.6 mcg/kg on Day 1 only. MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 17%. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 4 absolute neutrophil count (ANC) anemia or thrombocytopenia; grade 4 ANC lasting > 7 days; grade ≥ 3 febrile neutropenia; grade ≥ 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), total bilirubin, and creatinine; delay in starting the 2nd cycle of mFOLFIRINOX by > 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4. Note: the third and lowest dose level was not reached.	2 cycles of 14 days
Phase II: Overall Survival	Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. Assessed using the logrank test.	From date of registration to date of death due to any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) (Phase II)	Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.	From date of registration to date of death due to any cause, assessed up to 3 years
Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial)	Objective tumor response rate (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions	Up to 3 years
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living e.g. bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event	Duration of treatment and follow up until death or 3 years post registration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Antigen (CA) 19-9 Levels	Explore correlation of maximum decrease in CA 19-9 levels to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response.	Within 2 years of the end of the study
Plasma Expression of Hyaluronan (HA)		Within 2 years of end of study
Tumor Expression of HA		Within 2 years of end of study

Collaborators and Investigators

• Sponsor: SWOG Cancer Research Network
• Collaborators: National Cancer Institute (NCI); Halozyme Therapeutics
• Investigators: Study Chair: Ramesh K Ramanathan, M.D., Virginia G. Piper Cancer Center

Publications and helpful links

General Publications

• Ramanathan RK, McDonough SL, Philip PA, Hingorani SR, Lacy J, Kortmansky JS, Thumar J, Chiorean EG, Shields AF, Behl D, Mehan PT, Gaur R, Seery T, Guthrie KA, Hochster HS. Phase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313. J Clin Oncol. 2019 May 1;37(13):1062-1069. doi: 10.1200/JCO.18.01295. Epub 2019 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2014
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): November 9, 2023

Study Registration Dates

• First Submitted: September 30, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimated): October 9, 2013

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: S1313 (Other Identifier: SWOG); U10CA180888 (U.S. NIH Grant/Contract); NCI-2013-01776 (Other Identifier: NCI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No