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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


Phase 1
18 Years
N/A
Open (Enrolling)
Female
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)

Outcome Time Frame:

Up to day 42

Safety Issue:

Yes

Principal Investigator

Katherine Bell-McGuinn

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-03730

NCT ID:

NCT00989651

Start Date:

October 2009

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Brenner Tumor
  • Carcinoma
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Cystadenocarcinoma
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Carcinoma, Endometrioid
  • Cystadenocarcinoma, Mucinous
  • Cystadenocarcinoma, Serous
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Johns Hopkins University Baltimore, Maryland  21205
Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
Washington University School of Medicine Saint Louis, Missouri  63110
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Franklin Square Hospital Center Baltimore, Maryland  21237
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
MetroHealth Medical Center Cleveland, Ohio  44109
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240
University of Virginia Charlottesville, Virginia  22908
Case Western Reserve University Cleveland, Ohio  44106
Riverside Methodist Hospital Columbus, Ohio  43214
Virginia Commonwealth University Richmond, Virginia  
Hillcrest Hospital Cancer Center Mayfield Heights, Ohio  44124
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Women and Infants Hospital Providence, Rhode Island  02905
University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora, Colorado  80045
Georgia Health Sciences University Augusta, Georgia  30912
Gynecologic Oncology Group Philadelphia, Pennsylvania  19103