Know Cancer

or
forgot password

A PHASE I PHARMACOKINETIC STUDY OF INTRAPERITONEAL CTEP-SUPPLIED AGENT BORTEZOMIB (PS-341, NSC 681239, IND# 58443) AND CARBOPLATIN (NSC# 241240) IN PATIENTS WITH PERSISTENT OR RECURRENT OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Brenner Tumor, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mixed Epithelial Carcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Serous Cystadenocarcinoma, Ovarian Undifferentiated Adenocarcinoma, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

Thank you

Trial Information

A PHASE I PHARMACOKINETIC STUDY OF INTRAPERITONEAL CTEP-SUPPLIED AGENT BORTEZOMIB (PS-341, NSC 681239, IND# 58443) AND CARBOPLATIN (NSC# 241240) IN PATIENTS WITH PERSISTENT OR RECURRENT OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER


PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of
intraperitoneal (IP) bortezomib (BTZ) when administered with IP carboplatin in women with
epithelial ovarian, fallopian tube, or primary peritoneal cancer that is persistent or
recurrent and who have failed primary therapy and at least one second-line therapy.

II. To examine the safety of administering BTZ in combination with carboplatin by the IP
route.

SECONDARY OBJECTIVES:

I. To estimate objective tumor response rate as determined by Response Evaluation Criteria
in Solid Tumors (RECIST) 1.1 criteria.

II. To determine the pharmacokinetic profile of BTZ and carboplatin when administered
intraperitoneally once every 21 days.

III. To characterize the frequency of carboplatin hypersensitivity reactions (HSR) when
administered as an intraperitoneal infusion in the context of recurrent ovarian cancer.

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

Patients receive bortezomib intraperitoneal (IP) and carboplatin IP on day 1. Treatment
repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
toxicity. Plasma and peritoneal fluid samples are collected at baseline and periodically
during the first course of therapy for pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 1 year.


Inclusion Criteria:



- Histologically or cytologically confirmed ovarian epithelial, fallopian tube, or
primary peritoneal cancer, including one of the following epithelial cell types*:

- Serous adenocarcinoma

- Endometrioid adenocarcinoma

- Mucinous adenocarcinoma

- Undifferentiated carcinoma

- Clear cell adenocarcinoma

- Mixed epithelial carcinoma

- Transitional cell carcinoma

- Malignant Brenner tumor

- Adenocarcinoma not otherwise specified

- Persistent or recurrent disease (either "platinum-sensitive" or platinum-resistant")

- Has failed primary therapy AND 1-2 second-line therapies

- No more than 3 prior second-line therapies in the recurrent disease setting

- Measurable or detectable disease

- Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension with the following:

- Lesion must be ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical
exam, OR ≥ 20 mm by chest x-ray

- Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI

- Detectable disease defined as any of the following:

- CA-125 baseline values of ≥ 2 times upper limit of normal

- Ascites and/or pleural effusion attributed to tumor

- Solid and/or cystic abnormalities on radiographic imaging that do not meet
RECIST 1.1 definitions for target lesions

- No synchronous primary endometrial cancer or history of primary endometrial cancer
unless the primary origin of the recurrent or persistent tumor is ovarian or
peritoneal AND all of the following criteria are met:

- Stage of endometrial cancer is ≤ IB

- No more than superficial myometrial invasion without vascular or lymphatic
invasion

- No poorly differentiated subtypes, including papillary serous, clear cell, or
other FIGO grade 3 lesions

- No known brain metastases

- 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 normal

- Calculated creatinine clearance > 50 mL/min

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- SGOT ≤ 3 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- INR ≤ 1.5 times ULN (or 2-3 for patients on a stable dose of therapeutic warfarin)

- PTT ≤ 1.5 times ULN

- Heparin, low molecular weight heparin, or alternative anticoagulants allowed

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other invasive malignancies within the past 5 years except nonmelanoma skin cancer
and localized breast cancer, including localized cancer of the breast, head and neck,
or skin adequately treated for > 3 years with no evidence of disease recurrence

- Neuropathy (sensory and motor) < grade 1

- No myocardial infarction within the past 12 months

- No new evidence of acute ischemia or conduction abnormalities by ECG

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection requiring parenteral antibiotics

- Acute hepatitis

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study
requirements

- No active infection requiring antibiotics except for uncomplicated urinary tract
infection

- No history of allergic reactions attributed to carboplatin or compounds of similar
chemical or biologic composition to bortezomib, including boron or mannitol

- No insulin-dependent diabetes

- No other concurrent investigational agents

- Must have had 1 prior platinum-based chemotherapeutic regimen for management of
primary disease containing carboplatin, cisplatin, or another organoplatinum compound
that included any of the following:

- Non-cytotoxic therapy

- Intraperitoneal therapy

- Consolidation therapy

- Extended therapy

- At least 1 prior cytotoxic regimen for the management of recurrent of persistent
disease

- Recovered from the effects of recent surgery, radiotherapy, or chemotherapy

- No prior bortezomib

- No prior cancer treatment that would contraindicate study treatment

- At least 1 week since prior hormonal therapy directed at the malignant tumor

- Continuation of hormone replacement therapy allowed

- At least 3 weeks since any other therapy directed at the malignant tumor, including
biological and immunologic agents

- No prior radiotherapy or chemotherapy for any abdominal or pelvic tumor other than
ovarian cancer

- More than 3 years since prior radiotherapy for localized cancer of the breast,
head and neck, or skin that remains free of recurrence or metastatic disease
allowed

- More than 3 years since prior adjuvant chemotherapy for localized breast cancer
that remains free of recurrence or metastatic disease allowed

- Concurrent ovarian estrogen and/or progestin replacement therapy for control of
menopausal symptoms allowed provided it is administered at the lowest effective
dose(s)

- No concurrent progestins for the management of anorexia

- No concurrent prophylactic growth factors (filgrastim, sargramostim, or pegfilgrastim

- No concurrent amifostine or other protective reagents

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Dose-limiting toxicities during the first course of therapy

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Don Dizon

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02014

NCT ID:

NCT01074411

Start Date:

April 2010

Completion Date:

Related Keywords:

  • Brenner Tumor
  • Ovarian Clear Cell Cystadenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mixed Epithelial Carcinoma
  • Ovarian Mucinous Cystadenocarcinoma
  • Ovarian Serous Cystadenocarcinoma
  • Ovarian Undifferentiated Adenocarcinoma
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity 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

University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Washington University School of MedicineSaint Louis, Missouri  63110
Hartford HospitalHartford, Connecticut  06102-5037
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
University of VirginiaCharlottesville, Virginia  22908
Case Western Reserve UniversityCleveland, Ohio  44106
Virginia Commonwealth UniversityRichmond, Virginia  
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Women and Infants HospitalProvidence, Rhode Island  02905