Carboplatin, Paclitaxel and Gemcitabine 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 February 2014 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: July 1, 2014
Last verified: February 2014

November 29, 2007
July 1, 2014
December 2007
December 2015   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Overall survival
Complete list of historical versions of study NCT00565851 on ClinicalTrials.gov Archive Site
  • Progression-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • 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 ]
  • Progression-free survival
  • Frequency and severity of adverse events
Not Provided
Not Provided
 
Carboplatin, Paclitaxel and Gemcitabine With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer
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. NCI-Supplied Agents: Bevacizumab (NSC #704865)

This randomized phase III trial is studying giving carboplatin, paclitaxel and gemcitabine together with or without bevacizumab after surgery to see how well it works in treating patients with recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab after surgery in treating patients with recurrent ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

PRIMARY OBJECTIVES:

I. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases the duration of overall survival in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer.

II. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases the duration of overall survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer.

SECOND OBJECTIVES:

I. To determine if the addition of bevacizumab to the second-line and maintenance phase of treatment increases the duration of progression-free survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or Fallopian tube cancer.

II. To prospectively determine the incidence of carboplatin and paclitaxel hypersensitivity in these patients undergoing retreatment with both agents as first recurrence therapy.

III. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases quality of life (QOL) of patients with recurrent platinum-sensitive ovarian epithelial cancer or primary peritoneal cavity cancer, as measured by the Functional Assessment of Cancer Therapy (FACT)-O trial outcome index and Rand SF-36 physical functioning scale.

IV. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases QOL relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum-sensitive ovarian epithelial cancer or primary peritoneal cavity cancer.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 4 treatment groups. Patients who are not candidates for surgical cytoreduction (i.e., those for whom complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking) are eligible to receive chemotherapy after randomization.

Patients who are eligible for surgery undergo abdominal exploration with cytoreduction and undergo tumor tissue collection and complete a quality of life questionnaire before and after surgery. All patients are then randomized to 1 of 4 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours or docetaxel IV over 1 hour and carboplatin IV over 60 minutes on day 1.

ARM II: Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1.

ARM III: Patients receive gemcitabine IV over 60 minutes on days 1and 8 and carboplatin as in arm I.

ARM IV: Patients receive gemcitabine IV as in arm III, bevacizumab IV and carboplatin IV as in arm II.

In all arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with measurable disease achieving a clinical response (CR) receive 6-8 courses of therapy. Patients with stable disease or partial regression receive a maximum of 6 courses.

Patients without measurable lesions as determined by a computed tomography (CT) scan prior to initiating study treatment continue therapy for 6 courses or, if CA-125 normalizes, for 2 cycles beyond CA-125 normalization, whichever is greater. Patients in arm II then receive a maintenance regimen comprising bevacizumab IV over 30-90 minutes. Treatment with bevacizumab alone repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brenner Tumor
  • Fallopian Tube Cancer
  • Ovarian Clear Cell Cystadenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mixed Epithelial Carcinoma
  • Ovarian Mucinous Cystadenocarcinoma
  • Ovarian Serous Cystadenocarcinoma
  • Ovarian Undifferentiated Adenocarcinoma
  • Primary Peritoneal Cavity Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Drug: docetaxel
    Given IV
    Other Names:
    • RP 56976
    • Taxotere
    • TXT
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • 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.
    Interventions:
    • Drug: paclitaxel
    • Drug: docetaxel
    • Drug: carboplatin
    • Other: laboratory biomarker analysis
    • Other: 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.
    Interventions:
    • Drug: paclitaxel
    • Drug: docetaxel
    • Drug: carboplatin
    • Biological: bevacizumab
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
  • Experimental: Arm III (gemcitabine, carboplatin)
    Patients receive gemcitabine IV over 60 minutes on days 1and 8 and carboplatin as in arm I.
    Interventions:
    • Drug: carboplatin
    • Drug: gemcitabine hydrochloride
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
  • Experimental: Arm IV (gemcitabine, bevacizumab, carboplatin)
    Patients receive gemcitabine IV as in arm III, bevacizumab IV and carboplatin IV as in arm II.
    Interventions:
    • Drug: carboplatin
    • Biological: bevacizumab
    • Drug: gemcitabine hydrochloride
    • Other: laboratory biomarker analysis
    • Other: quality-of-life assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
660
Not Provided
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologic diagnosis of ovarian epithelial carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent
  • 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 Tumor
    • Adenocarcinoma not otherwise specified
  • Patients must have had a complete response to front-line platinum-taxane therapy (at least 3 cycles) and a treatment-free interval without clinical evidence of progressive disease lasting at least 6 months

    • A complete response to front-line chemotherapy must include the following:

      • Negative physical exam
      • Negative pelvic exam
      • Normalization of CA125, if elevated at baseline
      • Negative radiographic assessment of 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
    • 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 (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) >= 1,500/mm^3 equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade1
  • Platelet count >= 100,000/mm^3 (Common Terminology Criteria for Adverse Events [CTCAE] Grade 0-1)
  • Creatinine (non-isotope dilution mass spectrometry [IDMS]) =< 1.5 times upper limit of normal (ULN)
  • Total bilirubin =< 1.5 times ULN
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) =< 2.5 times ULN (< 5.0 times ULN in the presence of liver metastasis)
  • Alkaline phosphatase =< 2.5 times ULN (< 5.0 times ULN in the presence of liver metastasis)
  • Patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
  • 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 signed an approved informed consent and authorization permitting release of personal health information
  • Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

Exclusion Criteria:

  • Patients who have more than one previous regimen of chemotherapy (maintenance therapy 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 they meet the inclusion criteria above
  • Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
  • 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 peripheral neuropathy >= grade 2
  • 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
  • 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; to date, no fetal studies in animal or humans have been performed; the possibility of harm to a fetus is likely; bevacizumab specifically inhibits VEGF, which is responsible for the formation of new blood vessels during development, and antibodies can cross the placenta; therefore, bevacizumab should not be administered to pregnant women; in addition, there are unknown immediate and long-term consequences of chemotherapy administration to these women; in addition, surgical exploration as mandated by randomization during pregnancy may cause imminent mortal consequences; further, it is not known whether bevacizumab is excreted in human milk; because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women; subjects will be apprised of the large potential risk to a developing fetus
  • Patients with other invasive malignancies, with the exception of nonmelanoma skin cancer, or patients who had (or have) any evidence of the other cancer present within the past 5 years or whose previous cancer treatment contraindicates this protocol therapy
  • 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
  • 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 the past 5 years of the first date of treatment on this study
  • Patients with clinically significant cardiovascular disease including any of the following:

    • Significant cardiac conduction abnormalities (e.g., PR interval > 0.24 sec or 2nd or 3rd degree atrioventricular [AV] block )
    • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction, cardiac arrhythmia, or unstable angina within the past 6 months
    • New York Heart Association (NYHA) grade II or greater congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Grade II or greater peripheral vascular disease except episodes of ischemia < 24 hrs in duration that are managed non-surgically and without permanent deficit
    • History of cerebrovascular accident (CVA) within the past 6 months
  • 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
Female
18 Years and older
No
United States,   Japan,   Korea, Republic of
 
NCT00565851
NCI-2009-00587, NCI-2009-00587, CDR0000546714, GOG-0213, GOG-0213, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Robert Coleman Gynecologic Oncology Group
National Cancer Institute (NCI)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP