Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00085358

Collaborator

Gynecologic Oncology Group (Other)

Enrollment

Locations

Arm

2.5

Patients Per Site

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of intraperitoneal infusions of carboplatin when given together with intravenous infusions of either docetaxel or paclitaxel followed by intraperitoneal paclitaxel in treating patients with stage II, stage III, or stage IV ovarian epithelial, fallopian tube, or primary peritoneal cavity carcinoma (cancer). Drugs used in chemotherapy, such as carboplatin, docetaxel, and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells

Condition or Disease	Intervention/Treatment	Phase
Brenner Tumor Fallopian Tube Cancer Ovarian Carcinosarcoma Ovarian Clear Cell Cystadenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mixed Epithelial Carcinoma Ovarian Mucinous Cystadenocarcinoma Ovarian Serous Cystadenocarcinoma Ovarian Undifferentiated Adenocarcinoma Primary Peritoneal Cavity Cancer Stage II Ovarian Epithelial Cancer Stage III Ovarian Epithelial Cancer Stage IV Ovarian Epithelial Cancer	Drug: carboplatin Drug: paclitaxel Drug: docetaxel Biological: bevacizumab	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of intraperitoneal (IP) carboplatin when given in combination with IV paclitaxel followed by IP paclitaxel in patients with stage III or IV ovarian epithelial, fallopian tube, or primary peritoneal cavity carcinoma.
Determine the MTD of IP carboplatin and IV docetaxel when given in combination with IP paclitaxel in these patients.
To determine the feasibility of the combination of IV paclitaxel, IP carboplatin and IV bevacizumab on day one followed by IP paclitaxel on day eight (Part C Only).
Determine the dose-limiting toxic effects and complications in patients treated with these regimens.
Evaluate the neurotoxicity of this regimen at each cycle using the FACT/GOG-NTX4 assessment tool to determine dose reduction in these patients.
Evaluate the techniques used for intraperitoneal catheter placement, surgical procedures, and reporting of outcomes in these patients.

OUTLINE: This is a multicenter, dose-escalation study of intraperitoneal (IP) carboplatin.

Patients in the dose-escalation phase are not eligible to enter the feasibility phase.

DOSE-ESCALATION PHASE (PART A or PART B): Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

FEASIBILITY PHASE (PART C): Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of Intravenous Paclitaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Docetaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Paclitaxel, Intraperitoneal Carboplatin, Intraperitoneal Paclitaxel and CTEP-Supplied Agent Bevacizumab (NSC 704865, IND 7921) in Patients With Previously Untreated Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab) Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given intraperitoneally Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Drug: paclitaxel Given IV or intraperitoneally Other Names: Anzatax Asotax TAX Taxol Drug: docetaxel Given IV Other Names: RP 56976 Taxotere TXT Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Arm

Intervention/Treatment

Experimental: Treatment (carboplatin, paclitaxel, docetaxel, bevacizumab)

Patients receive IP carboplatin on day 1, and paclitaxel IV over 3 hour (part A) or docetaxel IV over 1 hour (Part B) on day 1, and IP paclitaxel on day 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive IP carboplatin on day 1, paclitaxel IV on day 1, and IP paclitaxel on day 8 in course 1 as in part A dose-escalation phase. Beginning in course 2 and all subsequent courses, patients receive IP carboplatin on day 1, IV paclitaxel on day 1, and IP paclitaxel on day 8 as in the dose-escalation phase, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin

Given intraperitoneally

Other Names:

Carboplat

CBDCA

JM-8

Paraplat

Paraplatin

Drug: paclitaxel

Given IV or intraperitoneally

Other Names:

Anzatax

Asotax

TAX

Taxol

Drug: docetaxel

Given IV

Other Names:

RP 56976

Taxotere

TXT

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) of IV paclitaxel with IP carboplatin followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [3 weeks]
MTD of IV docetaxel with IP carboplatin followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0 [3 weeks]
MTD of IV paclitaxel with IP carboplatin and IV bevacizumab followed by IP paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0 [3 weeks]

Secondary Outcome Measures

Incidence of adverse events in patients given IV paclitaxel with IP carboplatin followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0 [12 weeks]
Incidence of adverse events in patients given of IV docetaxel with IP carboplatin followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0 [12 weeks]
Incidence of adverse events in patients given IV paclitaxel with IP carboplatin and IV bevacizumab followed by IP paclitaxel at the MTD, assessed by CTCAE v3.0 [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed fallopian tube, ovarian epithelial, or primary peritoneal carcinoma
Stage II-IV disease
The following epithelial cell types are allowed:
Carcinosarcoma
Serous adenocarcinoma
Endometrioid adenocarcinoma
Mucinous adenocarcinoma
Undifferentiated carcinoma
Clear cell adenocarcinoma
Mixed epithelial carcinoma
Transitional cell carcinoma
Malignant Brenner's tumor
Adenocarcinoma not otherwise specified
Must have undergone prior surgery for ovarian or peritoneal carcinoma within the past 12 weeks
Optimal (≤ 1 cm residual disease) or suboptimal residual disease following initial surgery
Must have a procedure for determining diagnosis of ovarian/peritoneal carcinoma with appropriate tissue for histologic evaluation
Synchronous primary endometrial cancer or prior endometrial cancer allowed provided the following criteria are met:
Stage ≤ IB
Less than 3 mm invasion without vascular or lymphatic invasion
No poorly differentiated subtypes (e.g., grade 3, clear cell, or papillary serous)
No epithelial ovarian carcinoma of low malignant potential (borderline carcinomas)
No CNS disease (e.g., seizures not controlled with standard medical therapy) or metastasis
GOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus) (applies to part C only)
PTT < 1.2 times the upper limit of normal (applies to part C only)
SGOT ≤ 2.5 times normal
Alkaline phosphatase ≤ 2.5 times normal
Bilirubin ≤ 1.5 times normal
Creatinine ≤ 1.5 times normal
No active bleeding
Abnormal cardiac conduction (e.g., bundle branch block or heart block) allowed provided disease has remained stable for the past 6 months
No unstable angina or myocardial infarction within the past 6 months
No neuropathy (sensory and motor) > CTCAE grade 1
Not pregnant or nursing
Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
No septicemia, severe infection, or acute hepatitis
No other invasive malignancy within the past 5 years except non-melanoma skin cancer or localized breast cancer
No circumstance that would preclude study participation
No history of allergic reaction to polysorbate 80 (e.g., etoposide or vitamin E)
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies (applies to part C only)
No clinically significant proteinuria
Must have urine protein-creatinine ratio (UPCR) < 1
No serious, non-healing wound, ulcer, or bone fracture (applies to part C only)
At least 3-6 months since prior abdominal fistula or gastrointestinal perforation and fully recovered (part C only)
No history of intra-abdominal abscess within the past 28 days (applies to part C only)
No active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels (applies to part C only)
No history or evidence (upon physical examination) of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases (applies to part C only)
No 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 (applies to part C only)
No significant traumatic injury within 28 days (applies to part C only)
No clinically significant cardiovascular disease, including any of the following (applies to part C only):
Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
Myocardial infarction or unstable angina < 6 months prior to registration
New York Heart Association (NYHA) Grade II or greater congestive heart failure
Serious cardiac arrhythmia requiring medication
CTCAE Grade 2 or greater peripheral vascular disease (at least brief (< 24 hrs) episodes of ischemia managed non-surgically and without permanent deficit)
History of CVA within the past six months
No clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition (applies to part C only)
No prior therapy with any anti-VEGF drug, including bevacizumab (applies to part C only)
No prior chemotherapy
Prior adjuvant chemotherapy for localized breast cancer allowed provided the therapy was completed at least 3 years before registration to study and the patient remains free of recurrent or metastatic disease
No prior radiotherapy
No prior cancer therapy that would contraindicate study treatment
No anticipation of invasive procedures, including any of the following (applies to part C only):
Major surgical procedure or open biopsy 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Medical Center At Irvine-Orange Campus	Orange	California	United States	92868
2	Colorado Gynecologic Oncology Group	Aurora	Colorado	United States	80010
3	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637-1470
4	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
5	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
6	Johns Hopkins University	Baltimore	Maryland	United States	21287-8936
7	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
8	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
9	Case Western Reserve University	Cleveland	Ohio	United States	44106
10	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
11	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
12	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
13	Cancer Care Associates-Midtown	Tulsa	Oklahoma	United States	74104
14	Cancer Care Associates-Yale	Tulsa	Oklahoma	United States	74136-1929
15	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103
16	Women and Infants Hospital	Providence	Rhode Island	United States	02905