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Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01081262
First received: March 4, 2010
Last updated: November 19, 2014
Last verified: November 2014
  Purpose

This randomized phase III trial studies carboplatin given together with paclitaxel with or without bevacizumab to see how well it works compared with oxaliplatin given together with capecitabine with or without bevacizumab as first-line therapy in treating patients with newly diagnosed stage II-IV, or recurrent (has come back) stage I epithelial ovarian or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, oxaliplatin, and capecitabine, 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, may block tumor growth in different ways by targeting certain cells. It is not yet known which regimen of combination chemotherapy given together with or without bevacizumab is more effective in treating epithelial ovarian cancer or fallopian tube cancer.


Condition Intervention Phase
Ovarian Mucinous Cystadenocarcinoma
Ovarian Mucinous Cystadenoma With Proliferating Activity
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Stage IA Fallopian Tube Cancer
Stage IA Ovarian Epithelial Cancer
Stage IB Fallopian Tube Cancer
Stage IB Ovarian Epithelial Cancer
Stage IC Fallopian Tube Cancer
Stage IC Ovarian Epithelial Cancer
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Epithelial Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Epithelial Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Epithelial Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Drug: carboplatin
Drug: paclitaxel
Drug: oxaliplatin
Drug: capecitabine
Biological: bevacizumab
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 GCIG Intergroup Multicenter Phase III Trial of Open Label Carboplatin and Paclitaxel +/- NCI-Supplied Agent: Bevacizumab (NSC #704865) Compared With Oxaliplatin and Capecitabine +/- Bevacizumab as First Line Chemotherapy in Patients With Mucinous Epithelial Ovarian or Fallopian Tube Cancer (MEOC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Examined using Kaplan-Meier curves. The main effect size will be quantified by the hazard ratio and 95% confidence interval. Multivariate regression will also be used to examine whether there is an interaction between oxaliplatin + capecitabine and bevacizumab.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Examined using Kaplan-Meier curves. The main effect size will be quantified by the hazard ratio and 95% confidence interval. Multivariate regression will also be used to examine whether there is an interaction between oxaliplatin + capecitabine and bevacizumab.

  • Response rates assessed by RECIST 1.1 [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    The comparison of response rates (proportion of patients with complete and partial response, stable and progressive disease) between treatment groups, will use a chi-square test. The difference in response rates between the groups and the odds ratio (with corresponding 95% confidence intervals) will also be calculated.

  • Incidence of adverse effects assessed by CTCAE version 4.0 [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Toxicity grades will be tabulated showing the maximum toxicity grade experienced by each patient. The proportions of patients experiencing a maximum grade of 3 or above will be compared between the treatment groups.

  • QOL scores assessed using FACT-O TOI and FACT-GOG/Neurotoxicity 4 [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Analysis of the QOL data will use the observed scores at each time point, where available. For simplicity, the change from baseline to each of time points will be examined. However, the main analysis will be a repeated measures analysis (for example, based on a mixed model, Proc Mixed in SAS) used to simultaneously compare all QOL scores between the two treatment groups.


Other Outcome Measures:
  • Numbers and percentages of patients with mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Will be tabulated. Interactions between the mutational status of the KRAS oncogene and treatment will be examined.


Estimated Enrollment: 332
Study Start Date: October 2010
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (carboplatin and paclitaxel)
Patients receive carboplatin IV over 30-60 minutes on day 1 and paclitaxel IV over 3 hours on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (oxaliplatin and capecitabine)
Patients receive oxaliplatin IV over 2-6 hours on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm III (carboplatin, paclitaxel, bevacizumab)
Patients receive carboplatin and paclitaxel IV as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes alone on day 1. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
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 IV (oxaliplatin, capecitabine, bevacizumab)
Patients receive oxaliplatin and capecitabine as in arm II, and bevacizumab as in arm III.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
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

  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 with a histologic diagnosis of mucinous adenocarcinoma of the ovary or fallopian tube with either optimal (=< 1 cm residual disease) or suboptimal residual disease following initial surgery; patients may have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or no measurable disease
  • All patients must have had appropriate surgery including appendectomy (unless patient has history of prior appendectomy) for ovarian or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage
  • Patients must have stage II-IV disease (new or recurrent-chemonaïve; no brain metastasis) or recurrent stage I disease (chemonaïve)
  • Newly diagnosed patients must begin protocol therapy within 10 weeks of primary debulking; for stage I recurrent patients (chemonaïve), they should begin protocol therapy within 14 days of randomization
  • Patients must have a negative colonoscopy within 1 year of enrolling in the study
  • Absolute neutrophil count (ANC) >= 1,500/mcl
  • White blood cell (WBC) count >= 3,000/mcl
  • Platelets >= 100,000/mcl
  • Hemoglobin (Hgb) >= 10 g/dl (can be post transfusion)
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) OR creatinine clearance > 50 cc/min
  • Bilirubin =< 1.5 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) =< to 2.5 x ULN
  • Alkaline phosphatase =< to 2.5 x ULN
  • Neuropathy (sensory and motor) =< Common Terminology Criteria for Adverse Events (CTCAE) grade 1
  • Urine dipstick for proteinuria < 2+; if urine dipstick is >= 2+, 24 hour urine must demonstrate =< 1 g protein in 24 hours OR patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
  • Prothrombin time (PT) =< 1.5 x ULN
  • Activated prothrombin time (APTT) =< 1.5 x ULN
  • Patients of childbearing potential must agree to practice an effective form of birth control during study treatment and for six months after completion of treatment
  • 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 Gynecologic Oncology Group (GOG) performance grade of 0, 1 or 2
  • Patients with life expectancy > 3 months

Exclusion Criteria:

  • Patients with known colon cancer or history of colon cancer
  • Patients with primary peritoneal carcinoma
  • 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 5 years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received chemotherapy, radiotherapy or any investigational treatment for a gynecologic cancer (does include breast cancer) or colorectal cancer prior to enrollment
  • Patients with a major surgical procedure anticipated during the course of the study; this includes but is not limited to: abdominal surgery (laparotomy or laparoscopy) such as colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery; please consult with the study chair prior to patient entry for any questions related to the classification of surgical procedures
  • Patients may have minor surgical procedures (i.e., mediport insertion) fine needle aspiration or core biopsies as long as it is performed > 7 days prior to the first date of bevacizumab therapy and there is no evidence of wound disruption or impaired healing
  • Patients with surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for fact that bevacizumab can be omitted from first cycle of chemotherapy)
  • Patients with a history of abdominal fistula or perforation within the past 12 months
  • Patients with a current, serious, non-healing wound, ulcer, or bone fracture; 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 known hypersensitivity to Chinese hamster cell products or other recombinant human or humanized antibodies
  • Patients with mixed epithelial ovarian cancer histology
  • Patients with tumors of low malignant potential
  • History or evidence of upon physical examination of central nervous system (CNS) disease, including history of primary brain tumor or any history of brain metastases, or seizures not controlled with standard medical therapy
  • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mm Hg; patients with a history of hypertension are permitted
  • Myocardial infarction or unstable angina within 12 months of the first date of bevacizumab therapy
  • New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction < 50% will be excluded from the study
  • Grade 1, category 2 or greater, peripheral vascular disease; patient cannot have anything worse than mild, symptomatic claudication with exercise
  • History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of bevacizumab therapy
  • History of pulmonary embolism or deep vein thrombosis in the past 6 months
  • Previous history of malabsorption or other conditions preventing oral treatment
  • Patients who are pregnant or nursing
  • Patients with acute hepatitis or active infection that requires parenteral antibiotics
  • Patients with active bleeding or pathologic conditions that carry a high risk of bleeding such as a known bleeding disorder, coagulopathy or tumor involving the major vessels
  • Patients taking warfarin
  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: NCT01081262

  Show 249 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: David Gershenson NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01081262     History of Changes
Other Study ID Numbers: NCI-2011-02516, NCI-2011-02516, CDR0000667089, GOG-0241, GOG-0241, U10CA180868, U10CA027469
Study First Received: March 4, 2010
Last Updated: November 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Cystadenocarcinoma, Mucinous
Cystadenoma
Cystadenoma, Mucinous
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adenocarcinoma
Adenoma
Adnexal Diseases
Carcinoma
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Cystic, Mucinous, and Serous
Ovarian Diseases
Urogenital Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Capecitabine
Carboplatin
Fluorouracil
Oxaliplatin

ClinicalTrials.gov processed this record on November 19, 2014