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 August 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: September 16, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: docetaxel
Drug: carboplatin
Biological: bevacizumab
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
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. NCI-Supplied Agents: Bevacizumab (NSC #704865)

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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 660
Study Start Date: December 2007
Estimated Primary Completion Date: December 2015 (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: 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
Other: laboratory biomarker analysis
Correlative studies
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.
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
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: 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.
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
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
Experimental: Arm IV (gemcitabine, bevacizumab, carboplatin)
Patients receive gemcitabine IV as in arm III, bevacizumab IV and carboplatin IV as in arm II.
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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 486 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Robert Coleman Gynecologic Oncology Group
  More Information

No publications provided

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, U10CA027469
Study First Received: November 29, 2007
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Cystadenocarcinoma, Serous
Cystadenocarcinoma, Mucinous
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Carcinoma
Carcinoma, Endometrioid
Brenner Tumor
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Endometrial Neoplasms
Uterine Neoplasms

ClinicalTrials.gov processed this record on September 30, 2014