Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00565851
First received: November 29, 2007
Last updated: August 22, 2016
Last verified: April 2016
  Purpose
This randomized phase III trial studies carboplatin, paclitaxel and gemcitabine hydrochloride when given together with or without bevacizumab after surgery to see how well it works in treating patients with ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer that has come back. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine hydrochloride 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. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab after surgery in treating patients with ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

Condition Intervention Phase
Clear Cell Adenocarcinoma
Fallopian Tube Clear Cell Adenocarcinoma
Fallopian Tube Endometrioid Adenocarcinoma
Fallopian Tube Mucinous Adenocarcinoma
Fallopian Tube Serous Adenocarcinoma
Mucinous Adenocarcinoma
Ovarian Brenner Tumor
Ovarian Clear Cell Adenocarcinofibroma
Ovarian Endometrioid Adenocarcinoma
Ovarian Seromucinous Carcinoma
Ovarian Serous Adenocarcinoma
Primary Peritoneal Serous Adenocarcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Undifferentiated Carcinoma
Undifferentiated Fallopian Tube Carcinoma
Undifferentiated Ovarian Carcinoma
Biological: Bevacizumab
Drug: Carboplatin
Drug: Docetaxel
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Quality-of-Life Assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary and Fallopian Tube Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The treatment regimens will be compared with a logrank procedure which includes all of the patients categorized by their randomly assigned treatment. The logrank test will be stratified by the secondary surgical debulking status (randomized to undergo cytoreduction, vs randomized to not undergo secondary cytoreduction vs not a candidate or did not consent to secondary surgical cytoreduction) and the duration of treatment free-interval prior to enrolling onto this study (6-12 months vs > 12 months).


Secondary Outcome Measures:
  • Change in QOL as measured by FACT-O and RAND-SF36 [ Time Frame: Baseline to up to 12 months after starting systemic therapy ] [ Designated as safety issue: No ]
    Descriptive statistics from the baseline QOL data will be calculated. These will include descriptions of the distribution of QOL scores (mean, standard deviation, median, etc.). For all patients the baseline scores will be calculated using the questionnaire completed prior to treatment cycle 1, except for those undergoing cytoreductive surgery. In that case, the baseline score is calculated using the questionnaire completed prior to surgery. Therefore, comparisons involving the patients who were allocated to surgery, the effects of time are confounded with effects of surgery.

  • Frequency and severity of adverse events assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    A logistic model will permit an estimate of the relative odds of grade 3 or worse adverse treatment effects for both randomized factors while adjusting for potential confounders like age. Deaths considered to be at least partially attributable to treatment will be reported and summarized.

  • Molecular and/or biochemical profiles [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 10 years ] [ Designated as safety issue: No ]
    A proportional hazards model will be fitted to the survival data. Apart from the randomized therapy, other factors such as: prior exposure to bevacizumab, histologic cell type, initial performance status, and age will be included in the model as potential confounders because there exists evidence that these factors may have an effect on survival in these patients.


Estimated Enrollment: 1038
Study Start Date: December 2007
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (paclitaxel, docetaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours or docetaxel IV over 1 hour and carboplatin over 30 minutes on day 1. Treatment repeats every 21 days.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)
Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm III (gemcitabine hydrochloride, carboplatin)
Patients receive gemcitabine hydrochloride IV over 60 minutes on days 1 and 8 and carboplatin as in Arm I.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin)
Patients receive gemcitabine hydrochloride IV as in Arm III, bevacizumab IV and carboplatin IV as in Arm II.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients enrolled after August 28, 2011 must be candidates for cytoreductive surgery and consent to have their surgical treatment determined by randomization
  • Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent
  • Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified (N.O.S.)
  • Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles)
  • A complete response to front-line chemotherapy must include: negative physical exam, negative pelvic exam and normalization of CA125, if elevated at baseline; although not required, any radiographic assessment of disease status (e.g. CT, magnetic resonance imaging [MRI], positron emission tomography [PET]/CT, etc) obtained following the completion of primary therapy should be considered negative for disease
  • All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e. bevacizumab)
  • Front-line treatment may include maintenance therapy following complete clinical or pathological response; however, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease; patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy
  • Patients must have clinically evident recurrent disease for the purpose of this study
  • Measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST]) is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be more than or equal to 20 mm when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm when measured by spiral CT
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to Common Toxicity Criteria for Adverse Events version (v)3.0 (CTCAE) grade 1
  • Platelets greater than or equal to 100,000/mm^3 (CTCAE grade 0-1)
  • Creatinine (non-isotope dilution mass spectrometry [IDMS]) =< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1
  • Total bilirubin =< 1.5 ULN (CTCAE grade 1)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) =< 2.5 times the upper limit of normal in the absence of liver metastasis; SGOT/AST < 5.0 times ULN in the presence of liver metastasis
  • Alkaline phosphatase =< 2.5 times the upper limit of normal in the absence of liver metastasis; alkaline phosphatase < 5.0 times ULN in the presence of liver metastasis
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
  • This eligibility criterion does not apply to patients enrolled after August 28, 2011; patients who are not candidates for surgical cytoreduction are eligible for the chemotherapy randomization; patients are not considered candidates for surgical cytoreduction if complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking
  • Patients must have met the pre-entry requirements as specified
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

Exclusion Criteria:

  • Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
  • Patients receiving concurrent immunotherapy, or radiotherapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded
  • Patients whom have already undergone secondary cytoreduction for recurrent disease are excluded
  • Patients with a prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and who subsequently developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer are eligible provided that they meet the criteria listed above
  • Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than ovarian, fallopian tube, and primary peritoneal) are excluded
  • Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
  • Patients with uncontrolled infection
  • Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
  • Patients with >= grade 2 peripheral neuropathy
  • Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds; patients with allergic (hypersensitivity) reactions to these chemotherapeutic agents are NOT excluded IF they were successfully retreated following a desensitization program or protocol
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are nursing are not eligible for this trial; bevacizumab should not be administered to nursing women
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major vessels
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with a 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 a history of stroke within 5 years of the first date of treatment on this study
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with clinically significant cardiovascular disease; this includes:

    • Patients with significant cardiac conduction abnormalities, i.e. PR interval > 0.24 seconds (sec) or 2nd or 3rd degree atrioventricular (AV) block
    • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
    • Myocardial infarction, cardiac arrhythmia 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
    • Grade II or greater peripheral vascular disease (exception: episodes of ischemia < 24 hours [hrs] in duration, that are managed non-surgically and without permanent deficit)
    • History of cerebrovascular attack (CVA) within six months
  • This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients who have had a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment on this study
  • Patients undergoing pre-treatment secondary cytoreduction will undergo therapy with bevacizumab on cycle #2
  • Patients undergoing pre-treatment surgery for purposes other than cytoreduction may also participate provided they meet eligibility; patients randomized to arms containing bevacizumab must wait a minimum of 28 days since that procedure to begin protocol treatment; patients who undergo an uncomplicated port placement must wait a minimum of 7 days to begin protocol treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565851

  Show 662 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Robert Coleman NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00565851     History of Changes
Other Study ID Numbers: NCI-2009-00587  NCI-2009-00587  CDR0000546714  GOG-0213  GOG-0213  U10CA180868  U10CA027469 
Study First Received: November 29, 2007
Last Updated: August 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Brenner Tumor
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Endometrial Neoplasms
Uterine Neoplasms
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Adenocarcinoma
Carcinoma
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Adenocarcinoma, Clear Cell
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on August 22, 2016