Trial record 1 of 1 for:    NCT00989651
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Carboplatin, Paclitaxel, Bevacizumab, and ABT-888 in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00989651
First received: October 2, 2009
Last updated: December 6, 2013
Last verified: December 2013

October 2, 2009
December 6, 2013
October 2009
July 2014   (final data collection date for primary outcome measure)
  • Dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase) [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]
  • DLTs occurring in the first 4 courses of treatment (feasibility phase) [ Time Frame: Up to day 84 ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase) [ Designated as safety issue: Yes ]
  • DLTs occurring in the first 4 courses of treatment (feasibility phase) [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00989651 on ClinicalTrials.gov Archive Site
  • Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, assessed up to 11 years ] [ Designated as safety issue: No ]
    Summarized using Kaplan-Meier plots.
  • Toxicity as assessed by NCI CTCAE v4.0 criteria [ Time Frame: Up to 30 days after last dose of drug treatment ] [ Designated as safety issue: Yes ]
  • Extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
  • Extent of PARP inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2 [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Genomic BRCA mutation status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Objective tumor response (complete and partial response) [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
  • Extent of PARP inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2 [ Designated as safety issue: No ]
  • Genomic BRCA mutation status [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Carboplatin, Paclitaxel, Bevacizumab, and ABT-888 in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
A PHASE I STUDY OF INTRAVENOUS CARBOPLATIN/PACLITAXEL OR INTRAVENOUS AND INTRAPERITONEAL PACLITAXEL/CISPLATIN IN COMBINATION WITH CONTINUOUS OR INTERMITTENT/ CTEP-SUPPLIED AGENT ABT-888 (NSC #737664) AND CTEP-SUPPLIED AGENT BEVACIZUMAB (NSC #704865) IN NEWLY DIAGNOSED PATIENTS WITH PREVIOUSLY UNTREATED EPITHELIAL OVARIAN, FALLOPIAN TUBE OR PRIMARY PERITONEAL CANCER

This phase I trial is studying the side effects and best dose of ABT-888 when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboplatin, paclitaxel, and bevacizumab together with ABT-888 may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 when administered with carboplatin, paclitaxel, and bevacizumab using 2 different treatment regimens in patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer.

II. To determine the feasibility of these regimens over 4 courses once the MTD is established.

III. To assess the toxicity of these regimens using NCI CTCAE v4.0 criteria.

SECONDARY OBJECTIVES:

I. To estimate the response rate in patients with measurable disease. II. To estimate the progression-free survival of patients treated with these regimens.

III. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2.

IV. To assess genomic BRCA mutation status in all patients and descriptively correlate it with toxicity and efficacy.

OUTLINE: This is a multicenter, dose-escalation study of ABT-888 followed by a feasibility study. Patients are sequentially assigned to 1 of 2 treatment regimens.

REGIMEN I: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes (beginning in course 2) on day 1. Patients also receive oral ABT-888 twice daily on days 1-21. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients also receive carboplatin, bevacizumab, and ABT-888 as in regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for biomarker analysis.

After completion of study treatment, patients are followed up periodically.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brenner Tumor
  • Ovarian Carcinosarcoma
  • Ovarian Clear Cell Cystadenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mixed Epithelial Carcinoma
  • Ovarian Mucinous Cystadenocarcinoma
  • Ovarian Serous Cystadenocarcinoma
  • Ovarian Undifferentiated Adenocarcinoma
  • Stage IIA Fallopian Tube Cancer
  • Stage IIA Ovarian Epithelial Cancer
  • Stage IIA Primary Peritoneal Cavity Cancer
  • Stage IIB Fallopian Tube Cancer
  • Stage IIB Ovarian Epithelial Cancer
  • Stage IIB Primary Peritoneal Cavity Cancer
  • Stage IIC Fallopian Tube Cancer
  • Stage IIC Ovarian Epithelial Cancer
  • Stage IIC Primary Peritoneal Cavity Cancer
  • Stage IIIA Fallopian Tube Cancer
  • Stage IIIA Ovarian Epithelial Cancer
  • Stage IIIA Primary Peritoneal Cavity Cancer
  • Stage IIIB Fallopian Tube Cancer
  • Stage IIIB Ovarian Epithelial Cancer
  • Stage IIIB Primary Peritoneal Cavity Cancer
  • Stage IIIC Fallopian Tube Cancer
  • Stage IIIC Ovarian Epithelial Cancer
  • Stage IIIC Primary Peritoneal Cavity Cancer
  • Stage IV Fallopian Tube Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Stage IV Primary Peritoneal Cavity Cancer
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Drug: carboplatin
    Given IV
    Other Names:
    • Carboplat
    • CBDCA
    • JM-8
    • Paraplat
    • Paraplatin
  • Biological: bevacizumab
    Given orally
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: veliparib
    Given IV
    Other Name: ABT-888
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Regimen I (paclitaxel, carboplatin, bevacizumab)
    Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes (beginning in course 2) on day 1. Patients also receive oral ABT-888 twice daily on days 1-21. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: paclitaxel
    • Drug: carboplatin
    • Biological: bevacizumab
    • Other: laboratory biomarker analysis
  • Experimental: Regimen II (paclitaxel, carboplatin, bevacizumab, veliparib)
    Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients also receive carboplatin, bevacizumab, and ABT-888 as in regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: paclitaxel
    • Drug: carboplatin
    • Biological: bevacizumab
    • Drug: veliparib
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
96
Not Provided
July 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed newly diagnosed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including one of the following histologic cell types:

    • Serous adenocarcinoma
    • Endometrioid adenocarcinoma
    • Mucinous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial adenocarcinoma
    • Transitional cell carcinoma
    • Malignant Brenner tumor
    • Adenocarcinoma not otherwise specified
    • Carcinosarcoma
  • Stage II-IV disease defined surgically with either optimal (≤ 1 cm) or suboptimal residual disease
  • Has undergone initial surgery for diagnosis, staging, and cytoreduction within the past 1-12 weeks
  • No current diagnosis of borderline ovarian epithelial tumor (formerly "tumors of low malignant potential") or recurrent invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with surgery only (e.g., stage IA or IB low-grade ovarian epithelial or fallopian tube cancers)

    • Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently developed an unrelated, new invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer are eligible provided they have not received prior chemotherapy for any ovarian tumor
  • No prior or synchronous primary endometrial cancer, unless all of the following criteria are met:

    • Disease stage ≤ IB
    • No more than superficial myometrial invasion
    • No vascular or lymphatic invasion
    • No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions
  • No history or evidence of primary brain tumor or brain metastases by physical exam
  • GOG performance status 0-2
  • ANC ≥ 1,500/mm^3 (not induced or supported by granulocyte colony-stimulating factors)
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Albumin ≥ 3.0 g/dL
  • PT/INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin)
  • PTT < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No clinically significant proteinuria (i.e., urine protein:creatinine ratio ≥ 1.0)
  • No neuropathy (sensory and motor) > CTCAE grade 1
  • No acute hepatitis or active infection requiring parenteral antibiotics
  • No serious non-healing wound, ulcer, or bone fracture

    • Patients with granulating incisions healing by secondary intention are eligible provided there is no evidence of fascial dehiscence or infection and the patient undergoes weekly wound examinations
  • No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
  • No clinical symptoms or signs of GI obstruction and/or requirement for parenteral hydration or nutrition
  • No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Peripheral ischemia ≥ CTCAE grade 2 (at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)
  • No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • No seizures not controlled with standard medical therapy or other evidence of CNS disease by physical exam
  • No other invasive malignancies within the past 5 years, except for nonmelanoma skin cancer and localized cancer of the breast or head and neck
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No significant traumatic injury within the past 28 days
  • See Disease Characteristics
  • No prior cancer treatment that would contraindicate study therapy
  • More than 5 years since prior chemotherapy for any abdominal or pelvic tumor

    • Prior adjuvant chemotherapy for localized breast cancer is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgical procedure
Female
18 Years and older
No
Not Provided
United States
 
NCT00989651
NCI-2011-03730, NCI-2011-03730, CDR0000656038, GOG-9923, GOG-9923, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Katherine Bell-McGuinn Gynecologic Oncology Group
National Cancer Institute (NCI)
December 2013

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