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Eligibility
for females ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started

Description

Summary

This phase III clinical trial studies two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. Bevacizumab is a type of drug called a monoclonal antibody and blocks tumor growth by stopping the growth of blood vessels that tumors need to grow. It is not yet known whether giving paclitaxel with combination chemotherapy once every three weeks is more effective than giving paclitaxel once a week in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

Official Title

A Phase III Trial of Every-3-Weeks Paclitaxel Versus Dose Dense Weekly Paclitaxel in Combination With Carboplatin With or Without Concurrent and Consolidation Bevacizumab (NSC #704865) in the Treatment of Primary Stage II, III or IV Epithelial Ovarian, Peritoneal or Fallopian Tube Cancer and ACRIN 6695: Perfusion CT Imaging to Evaluate Treatment Response in Patients Participating in GOG-0262

Details

PRIMARY OBJECTIVES:

I. To determine if the weekly paclitaxel regimen increases the time until first progression or death (progression-free survival [PFS]) compared to the every-3-week paclitaxel regimen in women with primary stage II, III or IV epithelial ovarian, peritoneal or fallopian tube cancer who are receiving carboplatin with or without bevacizumab.

SECONDARY OBJECTIVES:

I. To determine if the weekly paclitaxel increases the duration of overall survival compared to the every-3-week paclitaxel when combined with carboplatin with or without bevacizumab.

II. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to the incidence of severe or serious adverse events when it is combined with carboplatin with or without bevacizumab.

III. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to patients' self-reported quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O)-Trial Outcome Index (TOI), when paclitaxel is combined with carboplatin with or without bevacizumab. (As of 02/08/2012, the QOL portion of this study is complete; patients enrolled after this date will not have QOL assessments)

TERTIARY OBJECTIVES:

I. To evaluate single nucleotide polymorphisms (SNPs) associated with progression-free survival and toxicity in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer using genome wide association studies (GWAS).* II. To evaluate genomic signatures in tumor tissues which are predictive for patient survival in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer.* III. To evaluate the association between serum and plasma biomarkers and response to anti-angiogenesis therapy in advanced stage epithelial ovarian, peritoneal, and fallopian tube cancer.*

NOTE: *As of 02/08/2012, the translational research (TR) portion of this study is complete; patients enrolled after this date will not have TR specimens collected.

IMAGING PRIMARY OBJECTIVES:

I. To determine whether larger changes in the tumor perfusion parameters from baseline timepoint (T0) to early-therapy T2 are prognostic of higher progression-free survival (PFS) rate at 6 months (PFS-6) from enrollment in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.*

IMAGING SECONDARY OBJECTIVES:

I. To determine whether larger changes in tumor perfusion parameters from baseline T0 to intermediate T1 and from T1 to T2 are prognostic of higher PFS-6 in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.* II. To determine whether larger changes in tumor perfusion parameters values from T0 to T1, T0 to T2, and T1 to T2 are prognostic of better overall survival in all treatment arms. III. To assess the association between changes in tumor perfusion parameters before and after chemotherapy initiation (T0 to T1) and subsequent best tumor response according to standard anatomic Response Evaluation Criteria in Solid Tumors (RECIST). IV. To assess the association between tumor perfusion parameters before chemotherapy and subsequent best tumor response according to RECIST, PFS-6, and overall survival. V. To test the assumption that tumor perfusion parameters are reliable, user-independent, and reproducible parameters of tumor microvascular characteristics; a subgroup of 15 patients will have repeat computed tomography (CT) perfusion studies at the intermediate T1 time point.**

NOTE: *Patients enrolled after February 8, 2012 must participate in the ACRIN 6695 component at ACRIN-qualified institutions.

OUTLINE: Patients are randomized to 1 of 2 treatment arms (beginning on 04-30-2012, the trial is no longer randomized and the chemotherapy regimen is selected and declared prior to enrolling in the study).

ARM I (adjuvant chemotherapy suboptimally debulked): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.

ARM II (neoadjuvant chemotherapy with interval cytoreductive surgery): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.

Patients in both arms may receive optional** bevacizumab IV over 30-90 minutes on day 1 beginning in course 2. Courses of bevacizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients in Arm II receive bevacizumab during courses 2, 5, and 6 only.

NOTE: **Before enrolling onto this study, each patient chooses whether the study treatment will include concurrent and maintenance bevacizumab.

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

Keywords

Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Malignant Ovarian Mixed Epithelial Tumor Ovarian Brenner Tumor Ovarian Clear Cell Adenocarcinofibroma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Adenocarcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Primary Peritoneal Serous Adenocarcinoma Stage IIA Fallopian Tube Cancer Stage IIA Ovarian Cancer Stage IIB Fallopian Tube Cancer Stage IIB Ovarian Cancer Stage IIC Fallopian Tube Cancer Stage IIC Ovarian Cancer Stage IIIA Fallopian Tube Cancer Stage IIIA Ovarian Cancer Stage IIIA Primary Peritoneal Cancer Stage IIIB Fallopian Tube Cancer Stage IIIB Ovarian Cancer Stage IIIB Primary Peritoneal Cancer Stage IIIC Fallopian Tube Cancer Stage IIIC Ovarian Cancer Stage IIIC Primary Peritoneal Cancer Stage IV Fallopian Tube Cancer Stage IV Ovarian Cancer Stage IV Primary Peritoneal Cancer Undifferentiated Ovarian Carcinoma Paclitaxel Albumin-Bound Paclitaxel Bevacizumab Carboplatin Endothelial Growth Factors Antibodies, Monoclonal Antibodies Immunoglobulins Immunoglobulin G

Eligibility

You can join if…

Open to females ages 18 years and up

  • Primary Surgery and Neoadjuvant Chemotherapy with Interval Cytoreductive Surgery

Patients:

  • Patients must have measurable disease; at least one target lesion must have a minimum length of 1 cm in both the long and short axis (determined at the local site); for primary surgery patients, if no radiographic evidence of measurable disease is obtained prior to registration this can be based on surgical findings; imaging then would need to be completed in the 14 days between Gynecology Oncology Group (GOG)registration and chemotherapy initiation
  • After GOG registration, the American College of Radiology [ACR] Imaging Core Laboratory will confirm target lesion as required per protocol; the GOG-eligibility (RECIST) scan and baseline T0 perfusion CT scans will be reviewed prior to the intermediate T1 perfusion CT time point
  • Primary Surgery Patients:
  • Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary carcinoma or fallopian tube cancer, stage II -IV suboptimally debulked (any residual disease> 1 cm); International Federation of Gynecology and Obstetrics (FIGO) stage is assessed following the completion of initial abdominal surgery, appropriate imaging studies and with appropriate tissue available for histologic evaluation; the minimum surgery required is an abdominal surgery providing tissue for histologic evaluation and establishing and documenting the primary site and stage; if additional surgery was performed, it should have been in accordance with appropriate surgery for ovarian or peritoneal carcinoma described in the GOG Surgical Procedures Manual
  • Neoadjuvant Chemotherapy (NAC) with Interval Cytoreductive Surgery (ICS) Patients:
  • For patients undergoing NAC-ICS, a core tissue (not fine needle aspiration) biopsy is required; the tissue must be consistent with a Müllerian origin; patients will require documentation of at least stage II or extraovarian sites of disease acquired via imaging or surgery (without attempt at cytoreduction)
  • Patients with the following histologic epithelial cell types are eligible: serous,endometrioid, clear cell, mucinous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.); however, the histologic features of the tumor must be compatible with a primary Müllerian epithelial adenocarcinoma;patients may have co-existing fallopian tube carcinoma in-situ so long as the primary origin of invasive tumor is ovarian, peritoneal or fallopian tube; of note, patients with clear cell and mucinous tumors will be eligible unless there is a higher priority protocol
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl; this ANC cannot have been induced or supported by granulocyte colony stimulating factors
  • Platelets greater than or equal to 100,000/mcl
  • Creatinine =< 1.5 x institutional upper limit normal (ULN)
  • Bilirubin less than or equal to 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN
  • Neuropathy (sensory or motor) less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 1
  • Patients must have a GOG performance status of 0, 1, or 2
  • Patients must be entered within 12 weeks of diagnostic/staging surgery
  • Patients who have met the pre-entry requirements
  • An approved informed consent and authorization permitting release of personal health information and must be signed by the patient or guardian
  • Only applies for patients who elect to receive bevacizumab:
  • Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time, but not high-dose progestins for management of anorexia while on protocol-directed therapy or prior to disease progression due to thrombophlebitis risk
  • 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 thromboembolus) and a partial prothrombin time (PTT) < 1.2 times the upper limit of normal; (heparin, lovenox or alternative anticoagulants are acceptable)
  • All patients enrolled into GOG-0262 at sites where ACRIN 6695 is open will be enrolled in the advanced imaging protocol; patients receiving adjuvant or neoadjuvant chemotherapy are eligible for ACRIN 6695; the following sentence does not apply to those patients entered after 02/08/2012: if a patient declines to participate in the perfusion imaging portion of the protocol, a clinical rationale for declination of imaging form will be completed as part of the data submission for ACRIN 6695
  • ACRIN 6695 Eligible Patients:
  • Confirmation of ACRIN 6695 eligibility after the baseline T0 perfusion computed tomography (CT) will be assessed by the ACR Imaging Core Lab: At least one target lesion must have a minimum length of 1 cm in both the long and short axis(as determined by the local site), at least half of the target lesion must have attenuation greater than or equal to 10 Hounsfield Units (HU) on the unenhanced CT, and at least half of the lesion must have maximum enhancement greater than or equal to 5 HU in the perfusion CT scan (as determined by the ACR Imaging Core Lab)

You CAN'T join if...

  • Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly"tumors of low malignant potential") or recurrent invasive epithelial ovarian,primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage I-A or I-B low grade epithelial ovarian or fallopian tube cancers) are not eligible; patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible,provided that they have not received prior chemotherapy for any ovarian tumor
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three 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 ovarian, primary peritoneal or fallopian tube cancer; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian, fallopian tube or peritoneal primary cancer
  • Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions
  • With the exception of non-melanoma skin cancer, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy
  • Patients with acute hepatitis or active infection that requires parenteral antibiotics
  • Patients with clinically significant cardiovascular disease; this includes:
  • Myocardial infarction or unstable angina < 6 months prior to registration
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
  • 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 bevacizumab therapy
  • Patients who have received prior therapy with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab
  • Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator should feel free to consult the Statistical and Data Center (SDC)randomization desk for uncertainty in this regard
  • Patients with known allergy to cremophor or polysorbate 80
  • Only applies to patients who elect to receive bevacizumab:
  • Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations
  • 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 with history or evidence upon physical examination of central nervous system(CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA,stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study
  • Patients with CTCAE grade 2 or greater peripheral vascular disease (at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)
  • Patients with a history of CVA within six months
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • Patients with clinically significant proteinuria; urine protein should be screened by urine protein-creatinine ratio (UPCR); the UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection; specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urine collection;obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24-hour urine); send sample to lab with request for urine protein and creatinine levels (separate requests); the lab will measure protein concentration(mg/dL) and creatinine concentration (mg/dL); the UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR < 1.0 to allow participation in the study
  • Patients with or with anticipation of invasive procedures as defined below:
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy (cycle 2)
  • Major surgical procedure anticipated during the course of the study; this includes, but is not limited to abdominal surgery (laparotomy or laparoscopy)prior to disease progression such as colostomy or enterostomy reversal,secondary cytoreductive surgery, or second look surgery; please consult with the SDC Randomization Desk prior to patient entry for any questions related to the classification of surgical procedures
  • Any tissue biopsy, such as a core biopsy, within 7 days prior to the first date of bevacizumab therapy (cycle 2)
  • Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
  • Patients with metastasis tumor in the parenchyma of the liver or lungs with proximity to large vessels which could make the patients at high risk of lethal hemorrhage during treatment with bevacizumab (ie. hemoptysis, liver rupture)
  • ACRIN 6695 Ineligible Patients:
  • Patients with contraindication to iodinated contrast for perfusion CT imaging
  • Patients who receive Metformin within 48 hours before perfusion CT imaging

Locations

  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, United States
  • Kaiser Permanente
    Fresno, California, 93720, United States
  • Kaiser Permanente Cancer Treatment Center
    South San Francisco, California, 94080, United States
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, United States
  • Bay Area Breast Surgeons Inc
    Emeryville, California, 94608, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Hematology and Oncology Associates-Oakland
    Oakland, California, 94609, United States
  • Tom K Lee Inc
    Oakland, California, 94609, United States
  • Marin Cancer Care Inc
    Greenbrae, California, 94904, United States
  • Highland General Hospital
    Oakland, California, 94602, United States
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California, 94611, United States
  • Kaiser Permanente-Oakland
    Oakland, California, 94611, United States
  • Doctors Medical Center- JC Robinson Regional Cancer Center
    San Pablo, California, 94806, United States
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, United States
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants-Castro Valley
    Castro Valley, California, 94546, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, United States
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, United States
  • John Muir Medical Center-Walnut Creek
    Walnut Creek, California, 94598, United States
  • John Muir Medical Center-Concord Campus
    Concord, California, 94520, United States
  • Stanford Cancer Institute
    Palo Alto, California, 94304, United States
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, United States
  • Kaiser Permanente-Fremont
    Fremont, California, 94538, United States
  • Valley Medical Oncology Consultants-Fremont
    Fremont, California, 94538, United States
  • El Camino Hospital
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, United States
  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California, 94531, United States
  • Rohnert Park Cancer Center
    Rohnert Park, California, 94928, United States
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, United States
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, United States
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, United States
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, United States
  • Kaiser Permanente-South Sacramento
    Sacramento, California, 95823, United States
  • South Sacramento Cancer Center
    Sacramento, California, 95823, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Kaiser Permanente - Sacramento
    Sacramento, California, 95825, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California, 95670, United States
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California, 95678, United States
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, United States
  • Sutter Roseville Medical Center
    Roseville, California, 95661, United States
  • Olive View-University of California Los Angeles Medical Center
    Sylmar, California, 91342, United States
  • Center of Hope at Renown Medical Center
    Reno, Nevada, 89502, United States
  • Renown Regional Medical Center
    Reno, Nevada, 89502, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California, 90048, United States
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California, 90095, United States
  • Long Beach Memorial Medical Center-Todd Cancer Institute
    Long Beach, California, 90806, United States
  • Women's Cancer Center of Nevada
    Las Vegas, Nevada, 89169, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT01167712
Phase
Phase 3
Study Type
Interventional
Last Updated
December 2015