Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III-IV Clear Cell Ovarian Cancer

A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864,) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus Consolidation as First-Line Therapy in the Treatment of Clear Cell Carcinoma of the Ovary

This phase II trial studies how well temsirolimus, carboplatin, and paclitaxel as first-line therapy works in treating patients with newly diagnosed stage III-IV clear cell ovarian cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be an effective treatment for ovarian cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Clear Cell Cystadenocarcinoma; Stage IV Ovarian Cancer; Stage III Ovarian Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Carboplatin; Drug: Paclitaxel; Drug: Docetaxel; Drug: Temsirolimus

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the activity of the study regimen as measured by the proportion of patients who are alive and progression-free for at least 12 months after study entry in patients with newly diagnosed stage III or IV clear cell ovarian cancer in the following populations: patients in the United States (U.S.) and worldwide (outside of Japan) and patients in Japan.

II. To compare progression-free survival in newly diagnosed stage III or IV clear cell ovarian cancer patients in patients in the U.S. and worldwide (outside of Japan) versus patients in Japan.

SECONDARY OBJECTIVES:

I. To characterize the duration of overall survival and progression-free survival in each population.

II. To examine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 in each population.

III. To estimate the rate of objective tumor response in patients with measurable disease.

TERTIARY OBJECTIVES:

I. To explore whether immunohistochemical (IHC) expression of components of the mammalian target of rapamycin (mTOR) signaling pathway (phosphatase and tensin homolog [PTEN], total and phosphorylated protein kinase B [Akt], as well as, ATP-binding cassette, sub-family C [CFTR/MRP], member 3 [ABCC3] [MRP3], ATPase, H+ transporting, lysosomal accessory protein 1 [AB CF2], cyclin E, and vascular endothelial growth factor [VEGF]) are associated with outcome, nationality or clinical characteristics.

II. To explore whether there is any differences in differential gene expression profiles between U.S. and worldwide (outside of Japan) versus Japanese patients.

OUTLINE:

Patients receive paclitaxel* intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity.

NOTE: * For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Matsuyama, Japan, 791-0280
    • Shikoku Cancer Center
  • Minami-ku, Japan, 811 1395
    • National Kyushu Cancer Center
  • Minato-ku, Tokyo, Japan, 105-8461
    • Jikei University School of Medicine
  • Osaka, Osaka, Japan, 589 8511
    • Kinki University
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Tokyo, Japan, 104 0045
    • National Cancer Center Hospital
  • Tottori, Japan, 680-8550
    • Tottori University
  • Aoba-ku
    • Sendai, Aoba-ku, Japan, 980-8574
      • Tohoku University School of Medicine
  • Hiroshima
    • Kure, Hiroshima, Japan, 737
      • Kure National Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyogo
    • Akashi-city, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University School of Medicine
  • Kagoshima
    • Kagoshima City, Kagoshima, Japan, 890-8760
      • Kagoshima City Hospital
  • Niigata
    • Niigata City, Niigata, Japan, 951-8520
      • Niigata University Medical and Dental Hospital
  • Okinawa
    • Nakagami-gun, Okinawa, Japan, 903-0215
      • University of the Ryukyus Hospital-Col Health Scnc
  • Suntou
    • Shizuoka City, Suntou, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 139-706
    • Korea Cancer Center Hospital
  • Daegu
    • Jung-Ku, Daegu, Korea, Republic of, 700-712
      • Keimyung University-Dongsan Medical Center
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center-Korea
  • Korea
    • Seoul, Korea, Korea, Republic of, 135-710
      • Samsung Medical Center
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family 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
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Hartford, Connecticut, United States, 06105
      • Saint Francis Hospital and Medical Center
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limted-Gynecologic Oncology
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Warrenville, Illinois, United States, 60555
      • Cadence Cancer Center in Warrenville
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Oncology Center
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium CCOP
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Maryland
    • Olney, Maryland, United States, 20832
      • Walter Reed Army Medical Center-Olney
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium CCOP
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Grand Blanc, Michigan, United States, 48439
      • Genesys Regional Medical Center
    • Grand Rapids, Michigan, United States, 49546
      • Gynecologic Oncology of West Michigan PLLC
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Niles, Michigan, United States, 49120
      • Michiana Hematology Oncology PC-Niles
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital-Joplin
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Women's Cancer Center of Nevada
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina At Chapel Hill
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center CCOP Research Base
  • Washington
    • Bellingham, Washington, United States, 98226
      • PeaceHealth Medical Group PC
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Mount Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Regional Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • 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, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98133
      • Northwest Hospital
    • Sequim, Washington, United States, 98384
      • Olympic Medical Cancer Care Center
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center-DHEC-Downtown
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must have stage III or IV clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections to confirm stage and histologic classification of cell type must be sent to Gynecologic Oncology Group (GOG) for central pathology review; immunohistochemical stained slides for ER and WT-1 antigen must be also be submitted to GOG for pathology review
• Patients who have met the pre-entry requirements
• Patients must have signed an approved informed consent and authorization permitting release of personal health information
• Patients with a GOG performance status of 0, 1, or 2
• Patients must be entered between 2 and 12 weeks after initial surgery; performed for the combined purpose of diagnosis, staging and cytoreduction
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
• Absolute neutrophil count >= 1,500/mcl
• Platelets >= 100,000/mcl
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times institutional upper limit of normal (< 5 times upper limit of normal [ULN] for subjects with liver metastases)
• Alkaline phosphatase =< 2.5 times institutional upper limit of normal (< 5 times ULN for subjects with liver metastases)
• Creatinine =< 1.5 x institutional upper limit of normal, grade 1 per CTCAE v. 4.0
• Cholesterol =< 350 mg/dL (fasting)
• Triglycerides =< 400 mg/dL (fasting)
• Albumin >= 3.0 g/dL
• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus)
• Partial thromboplastin time (PTT) < 1.2 times the upper limit of normal
• Neurologic function (sensory and motor) =< CTCAE grade 1

Exclusion Criteria:

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than five years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their clear cell ovarian cancer
• Patients with primary peritoneal and fallopian tube carcinoma are not eligible
• Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin
• Patients cannot be receiving enzyme-inducing antiepileptic drugs (enzyme-inducing antiepileptic drugs [EIAEDs]; e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's Wort; use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited; the appropriateness of use of such agents is left to physician discretion; strong CYP3A4 inhibitors are prohibited
• Patients receiving any investigational agents
• Patients with severely impaired lung function defined as a diffusion lung capacity for carbon monoxide (DLCO) =< 50% of the normal predicted value and/or oxygen (O2) saturation =< 88% at rest on room air
• Patients with symptomatic congestive heart failure of New York Heart Association class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days)
• Patients with baseline requirement for oxygen
• Patients with serious concomitant illness which, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol
• Patients who are pregnant or nursing; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of study therapies
• Patients with poorly controlled diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel); Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: * For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Paraplat; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Docetaxel; Given IV; Other Names: Taxotere; RP56976; Taxotere Injection Concentrate; Drug: Temsirolimus; Given IV; Other Names: Torisel; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan	Progression of target lesions (TL) was a >=20% increase in the sum of the diameters of TL, taking as reference the smallest sum on study (including the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must demonstrate an absolute increase >=5 mm. Progression of non-target lesions (NTL) as defined as appearance of >=1 new lesions or unequivocal progression of existing NTL. Unequivocal progression should not normally trump target lesion status; it must be representative of overall disease status change, not a single lesion increase. Clear progression of only NTL is exceptional, but the opinion of the treating physician should prevail in such circumstances, and the progression status should be later confirmed by a review panel (or Principal Investigator). Progression of TL, unequivocal progression of NTL, or new lesions constitutes progression. This description is abbreviated; see the RECIST 1.1 manuscript for further details.	Tumor scans were done every other cycle for the first 6 months; then every 3 months x2; then every 6 months thereafter; and at any other time if clinically indicated or signs suggestive of progressive disease or rising levels; for up to 5 years.
Compare Progression-free Survival in Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer Patients in Patients in the U.S. and Worldwide (Outside of Japan) Versus Patients in Japan.	Progression-free survival (PFS) was defined s the period from study entry until disease progression, death, or the last date of contact. Progression was based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Outcome measure data not reported because protocol stated "If the combination is declared active (i.e. HO is rejected) in one or both of the populations, the two populations will be compared with respect to PFS using a logrank test stratified by optimal/suboptimal disease status." The combination was not declared active in either population.	Tumor scans were done every other cycle for the first 6 months;then every 3 mnths x2;then every 6 mnths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggesting progressive dx or rising serum tumor marker le
Frequency and Severity of Toxicity	Grade 3 or higher adverse events were graded by CTC AE v4	Each cycle while on treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1	Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 mths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising tumor mark
Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.
Objective Tumor Response	Complete and Partial Tumor Response by RECIST 1.1. RECIST1.1 is a multi-page paper, and response is defined in the protocol across multiple pages, so it is not practical to define response here.	Every other cycle for first 6 months; then every 3 months for two years; then every six months for the next three years; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tu

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: John Farley, NRG Oncology

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 4, 2010
• First Submitted That Met QC Criteria: September 4, 2010
• First Posted (Estimate): September 8, 2010

Study Record Updates

• Last Update Posted (Actual): August 8, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Docetaxel; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Sirolimus
• Other Study ID Numbers: NCI-2011-02653 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA027469 (U.S. NIH Grant/Contract); CDR0000684262; GOG-0268 (Other Identifier: CTEP)