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Trial record 1 of 1 for:    NCT00989651
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Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal 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:
NCT00989651
First received: October 2, 2009
Last updated: November 25, 2014
Last verified: August 2014

October 2, 2009
November 25, 2014
October 2009
September 2020   (final data collection date for primary outcome measure)
  • Incidence of 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 ]
  • Incidence of 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 ]
    Tabulated by regimen and BRCA mutation status.
  • 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 by BRCA mutation status.
  • Incidence of toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
    Tabulated by regimen and by BRCA mutation status.
  • Change in PARP inhibition in peripheral blood mononuclear cells (PBMCs) [ Time Frame: Day 1 to day 22 (day 1 of course 1 to day 1 of course 2) ] [ Designated as safety issue: No ]
    PARP inhibition in PBMCs in each course (courses 1 and 2) and the change from course1 to course 2 will be summarized by dose level and regimen using descriptive statistics (e.g., mean, standard deviation, median, quartiles) and using graphs. In addition, linear models may be used to assess the association between PARP inhibition and dose level with transformations of the PARP inhibition as appropriate.
  • 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 Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, 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 studies the side effects and best dose of veliparib when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cells to repair themselves from damage and survive. 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, by stopping them from dividing, or by stopping them from spreading. Bevacizumab, a type of drug called a monoclonal antibody, blocks tumor growth by targeting certain cells and preventing the growth of tumor blood vessels. Giving veliparib together with carboplatin, paclitaxel, and bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when administered using continuous versus intermittent dosing schedules with intravenous carboplatin, paclitaxel and bevacizumab using two different treatment regimens; or with intraperitoneal cisplatin and intravenous and intraperitoneal paclitaxel and bevacizumab in women with newly diagnosed, previously untreated, epithelial ovarian, fallopian tube, or primary peritoneal cancer.

II. To determine the feasibility of these treatment regimens over four cycles in a 2-stage group sequential design once the MTD is established.

III. To assess the toxicity of these regimens using Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

SECONDARY OBJECTIVES:

I. To estimate the response rate (in measurable disease patients) and progression-free survival in patients treated with these treatment regimens.

TERTIARY OBJECTIVES:

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

II. To assess genomic breast cancer, early onset (BRCA) mutation status in all patients in regimens I and II with continuous ABT-888 dosing and descriptively correlate with toxicity and efficacy.

OUTLINE: This is a dose-escalation study of veliparib followed by a feasibility study. Patients are sequentially assigned to 1 of 3 treatment regimens.

REGIMEN I: Patients receive paclitaxel intravenously (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 veliparib orally (PO) twice daily (BID) 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 veliparib 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.

REGIMEN III: Patients receive paclitaxel IV over 3 hour on day 1 and intraperitoneally (IP) on day 8, and cisplatin IP on day 1 or 2. Patients also receive bevacizumab and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.

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
  • Malignant Ovarian Mixed Epithelial Tumor
  • Ovarian Brenner Tumor
  • Ovarian Carcinosarcoma
  • Ovarian Clear Cell Cystadenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mucinous Cystadenocarcinoma
  • Ovarian Serous Cystadenocarcinoma
  • Stage II Ovarian Cancer
  • Stage IIA Fallopian Tube Cancer
  • Stage IIA Ovarian Cancer
  • Stage IIB Fallopian Tube Cancer
  • Stage IIB Ovarian Cancer
  • Stage IIC Fallopian Tube Cancer
  • Stage IIC Ovarian Cancer
  • Stage IIIA Fallopian Tube Cancer
  • Stage IIIA Ovarian Cancer
  • Stage IIIA Primary Peritoneal Cancer
  • Stage IIIB Fallopian Tube Cancer
  • Stage IIIB Ovarian Cancer
  • Stage IIIB Primary Peritoneal Cancer
  • Stage IIIC Fallopian Tube Cancer
  • Stage IIIC Ovarian Cancer
  • Stage IIIC Primary Peritoneal Cancer
  • Stage IV Fallopian Tube Cancer
  • Stage IV Ovarian Cancer
  • Stage IV Primary Peritoneal Cancer
  • Undifferentiated Ovarian Carcinoma
  • Drug: Paclitaxel
    Given IV or IP
    Other Names:
    • Anzatax
    • TAX
  • Drug: Carboplatin
    Given IV
  • Biological: Bevacizumab
    Given IV
    Other Names:
    • Avastin
    • rhuMab-VEGF
  • Drug: Veliparib
    Given PO
    Other Name: ABT-888
  • Drug: Cisplatin
    Given IP
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Experimental: Regimen I (paclitaxel, carboplatin, bevacizumab, veliparib)
    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 veliparib PO BID 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
    • Drug: Veliparib
    • 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 veliparib 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
  • Experimental: Regimen III (paclitaxel, cisplatin, bevacizumab, veliparib)
    Patients receive paclitaxel IV over 3 hour on day 1 and IP on day 8, and cisplatin IP on day 1 or 2. Patients also receive bevacizumab and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Paclitaxel
    • Biological: Bevacizumab
    • Drug: Veliparib
    • Drug: Cisplatin
    • 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
September 2020   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with a histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, or carcinosarcoma stage II, III, or IV with either optimal (=< 1 cm residual disease) or suboptimal residual disease
  • All patients must have a procedure for determining diagnosis of epithelial ovarian, fallopian tube, primary peritoneal, or carcinosarcoma with appropriate tissue for histologic evaluation
  • Patients with the following histologic cell types are eligible:

    • Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor, adenocarcinoma not otherwise specified (N.O.S.) or carcinosarcoma
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to CTEP Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, grade 1; this ANC cannot have been induced or supported by granulocyte colony stimulating factors
  • Platelets greater than or equal to 100,000/mm^3
  • Regimens I and II: Creatinine =< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1

    • Regimen III: Creatinine no greater than the institutional upper limits of normal
  • Bilirubin less than or equal to 1.5 x ULN (CTEP CTCAE version 4.0, grade 1)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN (CTEP CTCAE version 4.0, grade 1)
  • Alkaline phosphatase less than or equal to 2.5 x ULN (CTEP CTCAE version 4.0, grade 1)
  • Albumin greater than or equal to 3.0 g/dL
  • Neuropathy (sensory and motor) less than or equal to CTEP CTCAE version 4.0, grade 1
  • Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) < 1.5 x ULN
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
  • Patients must be entered between 1 and 12 weeks after initial surgery performed for the combined purpose of diagnosis, staging and cytoreduction
  • Patients who have met the pre-entry requirements specified
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage IA or IB low-grade epithelial ovarian or fallopian tube cancers) are not eligible

    • NOTE: Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible, provided that they have not received prior chemotherapy for any ovarian tumor
  • Patients with synchronous primary endometrial cancer or a past history of endometrial cancer, unless all of the following conditions are met:

    • Stage not greater than IB
    • No more than superficial myometrial invasion
    • No 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 a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last five years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients with acute hepatitis or active infection that requires parenteral antibiotics
  • Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; 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 active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures or history of seizures, and/or any CNS metastases are ineligible
  • Patients with history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study are ineligible
  • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
  • Myocardial infarction or unstable angina < 6 months prior to registration
  • New York Heart Association (NYHA) class II or higher congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • CTEP CTCAE version 4.0, grade 2 or higher peripheral ischemia (brief [< 24 hrs] episode of ischemia managed non-surgically and without permanent deficit)
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • Patients with clinically significant proteinuria (urine protein creatinine ratio greater or equal to 1.0)
  • Patients with invasive procedures or anticipation of invasive procedures within the following timeframes as defined below:

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy (cycle 2)
    • Major surgical procedure anticipated during the course of the study
    • Core biopsy within 7 days prior to the first date of bevacizumab therapy (cycle 2)
  • Patients who are pregnant or nursing
  • Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration or nutrition
  • Patients with GOG performance status of 3 or 4
Female
18 Years and older
No
United States
 
NCT00989651
NCI-2011-03730, NCI-2011-03730, CDR0000656038, GOG-9923, GOG-9923, U10CA180868, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Katherine Bell-McGuinn NRG Oncology
National Cancer Institute (NCI)
August 2014

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