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A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of Intraperitoneal Carboplatin (NSC #214240) and Intravenous Paclitaxel (NSC # 673089) and Intravenous Paclitaxel, Intraperitoneal Carboplatin and NCI Supplied Intravenous Bevacizumab (NSC #704865, IND #7921) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma


Phase 1
18 Years
N/A
Not Enrolling
Female
Brenner Tumor, Fallopian Tube Cancer, 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

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Trial Information

A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of Intraperitoneal Carboplatin (NSC #214240) and Intravenous Paclitaxel (NSC # 673089) and Intravenous Paclitaxel, Intraperitoneal Carboplatin and NCI Supplied Intravenous Bevacizumab (NSC #704865, IND #7921) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of intraperitoneal carboplatin when administered
with paclitaxel during course 1, in patients with stage II-IV ovarian epithelial, primary
peritoneal, or fallopian tube cancer who had initial debulking surgery.

II. Determine the feasibility of this regimen in these patients. III. Determine the
feasibility of adding IV bevacizumab to this regimen in courses 2-6.

SECONDARY OBJECTIVES:

I. Determine the toxicity profile of this regimen in these patients. II. Determine the
toxicity profile of paclitaxel and bevacizumab IV in combination with intraperitoneal
carboplatin in these patients.

III. Determine the response rate (in patients with measurable disease who are in the
expanded cohort) and progression-free survival of patients treated with this regimen.

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

Patients receive paclitaxel IV over 3 hours followed by intraperitoneal carboplatin over 15
minutes on day 1 in course 1. Beginning in course 2, patients also receive bevacizumab IV
over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional
20-40 patients are treated at that dose level.

Patients are followed every 3 months for 1 year.


Inclusion Criteria:



- Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube
cancer

- Stage II-IV disease

- The following histologic epithelial cell types are eligible:

- Serous adenocarcinoma

- Mucinous adenocarcinoma

- Clear cell adenocarcinoma

- Transitional cell carcinoma

- Adenocarcinoma not otherwise specified

- Endometrioid adenocarcinoma

- Undifferentiated carcinoma

- Mixed epithelial carcinoma

- Malignant Brenner's tumor

- Optimal (≤ 1 cm residual disease) OR suboptimal residual disease after initial
debulking surgery (performed within the past 12 weeks)

- Synchronous primary endometrial cancer OR prior history of endometrial cancer allowed
provided all of the following are true:

- Stage IB disease or less

- Less than 3 mm invasion without vascular or lymphatic invasion

- No poorly differentiated subtypes, including the following:

- Papillary serous

- Clear cell

- Other FIGO grade 3 lesions

- No epithelial tumors of low malignant potential (borderline tumors)

- No CNS disease, including primary brain tumor, seizures not controlled with standard
medical therapy, or brain metastases by history or evidence upon physical examination
within the past 6 months

- Performance status - GOG 0-2

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- INR ≤ 1.5

- PTT < 1.2 times upper limit of normal (ULN)

- No active bleeding or pathologic conditions carrying high risk of bleeding (e.g.,
known bleeding disorder, coagulopathy, or tumor involving major vessels)

- AST ≤ 3 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 3 times ULN

- Bilirubin ≤ 1.5 times ULN

- No acute hepatitis

- Creatinine ≤ 2.0 mg/dL

- Urine protein-creatinine ratio < 1.0 OR protein 1.0 g by 24 hour urine collection

- Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed
provided the patient's cardiac status has been stable for ≥ 6 months before study
entry

- 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

- New York Heart Association class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease ≥ CTCAE grade 2 (at least brief (< 24 hrs) episodes
of ischemia managed non-surgically and without permanent deficit)

- No history of cerebrovascular accident (CVA, stroke), transient ischemic attack
(TIA) or subarachnoid hemorrhage within the past 6 months

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of bevacizumab therapy

- No neuropathy (sensory and motor) > grade 1

- No active infection requiring antibiotics

- No circumstances that would preclude study participation

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human or humanized antibodies

- No history of allergic reaction to polysorbate 80 (e.g., etoposide, vitamin E)

- No other invasive malignancies within the past 5 years except non-melanoma skin
cancer or localized breast cancer

- No serious, non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within 28 days prior to bevacizumab therapy

- No prior history of abdominal fistula or gastrointestinal perforation within the past
3-6 months

- Granulating incisions healing by secondary intention with no evidence of fascial
dehiscence or infection allowed but require weekly wound examinations

- No clinical symptoms or signs of gastrointestinal obstruction requiring parenteral
hydration and/or nutrition

- At least 28 days since intra-abdominal abscess and recovered

- At least 3 years since prior adjuvant chemotherapy for localized breast cancer

- Patients must remain free of recurrent or metastatic disease

- At least 3 years since prior radiotherapy for localized cancer of the breast, head
and neck, or skin

- Patient must remain free of recurrent or metastatic disease

- No prior radiotherapy to any portion of the abdominal cavity or pelvis

- No concurrent amifostine or other protective agents

- No concurrent major surgical procedure or open biopsy or within 28 days prior to
bevacizumab therapy

- No core biopsy within 7 days prior to bevacizumab therapy

- No prior therapy for this malignancy

- No prior cancer treatment that contraindicates study therapy

- No prior anti-VEGF drug, including bevacizumab

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of intraperitoneal carboplatin with intravenous paclitaxel, determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Outcome Time Frame:

3 weeks

Safety Issue:

Yes

Principal Investigator

Mark Morgan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00620

NCT ID:

NCT00079430

Start Date:

June 2004

Completion Date:

Related Keywords:

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

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
University of Washington Medical CenterSeattle, Washington  98195-6043
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Seattle Cancer Care AllianceSeattle, Washington  98109
Pacific Gynecology SpecialistsSeattle, Washington  98104
Riverside Methodist HospitalColumbus, Ohio  43214
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
M D Anderson Cancer CenterHouston, Texas  77030
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Cooper Hospital University Medical CenterCamden, New Jersey  08103
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Cancer Care Associates-MidtownTulsa, Oklahoma  74104
Women and Infants HospitalProvidence, Rhode Island  02905
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103