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A Phase I Study Evaluating the Safety and Tolerability of PS-341(Bortezomib)and Carboplatin in Patients With Platinum- and Taxane-Resistant Recurrent Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer

Phase 1
Not Enrolling
Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer

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Trial Information

A Phase I Study Evaluating the Safety and Tolerability of PS-341(Bortezomib)and Carboplatin in Patients With Platinum- and Taxane-Resistant Recurrent Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer

Bortezomib is a drug that turns off certain genes and proteins inside the cancer cell that
are responsible for cell growth. Researchers believe that when certain genes and proteins
are turned off, the ability of the cancer cell to survive is decreased.

Before treatment starts, participants will have a complete checkup, blood tests, a urine
test, a heart test, a chest x-ray, and either a CT scan or MRI scan. Women able to have
children must have a negative blood pregnancy test within 14 days of beginning treatment.
Blood tests and a complete checkup will also be done before each course of therapy and a
month after treatment ends. Approximately 2-3 teaspoons of blood will be obtained for
routine blood tests each time blood is drawn during this study.

Participants in this study will receive Bortezomib and carboplatin through a catheter (tube)
placed in a vein. This is Day 1 of therapy. Bortezomib is given first (over 5 to 10 seconds)
followed by carboplatin (over one hour). Bortezomib is then given alone on Days 4, 8, and
11. There is no treatment given on Days 12-28. One course of therapy is 28 days long and
includes one dose of carboplatin and 4 doses of Bortezomib. All treatment is given on an
outpatient basis at M. D. Anderson.

There are 4 different dose levels of Bortezomib being studied. The dose of Bortezomib that
participants receive will depend on when they are enrolled. It will also depend on whether
or not other participants had side effects from their treatment. Up to 6 patients could be
treated at each dose.

Before each course of therapy, participants will have a physical exam and blood tests. A CT
scan or MRI scan is repeated after Cycles 2 and 4 and at the end of treatment. Participants
who have a partial or complete response (the tumor shrinks by more than 50% or disappears
completely) will have a repeat CT or MRI 4 weeks later to confirm the response.

Participants may receive up to 8 courses of treatment. If the disease gets worse or if
intolerable side effects occur, participants will be taken off study.

This is an investigational study. Bortezomib is approved for use by the FDA, in patients
with multiple myeloma. Carboplatin is approved by the FDA, though its use with Bortezomib is
experimental. A total of 24 patients will take part in this study. All will be enrolled at
M. D. Anderson.

Inclusion Criteria:

- Patients must have histologically-confirmed ovarian cancer, primary peritoneal
cancer, or fallopian tube cancer with advanced and/or metastatic disease. All
patients must be considered platinum- and taxane- resistant.

- Platinum resistance is defined as:

1. Progression of disease during platinum or taxane chemotherapy, or

2. Progression of disease within 6 months of completing platinum or taxane

3. Failure to achieve a complete response, with persistent macroscopic disease,
after 6 cycles of chemotherapy, if the last two cycles had no measurable change
in disease status

- Patients may have had any number of prior chemotherapy regimens, except high dose
chemotherapy an/or peripheral blood stem cell transplantation (high dose: higher than
the standard doses of chemotherapy)

- Patients must have measurable disease.

- Zubrod performance status of < 2.

- Patients must give voluntary written informed consent before performance of any
study-related procedure not part of normal medical care.

- Adequate liver, renal and bone marrow function, defined as:

- Absolute neutrophil count (ANC) > 1.5 x 10^9/L.

- Platelets > 100 x 10^9/L

- Total bilirubin < 1.7 umol/L

- Alanine transaminase (ALT) and aspartate transaminase (AST) < 1.5 x Upper Limits
of Normal (ULN)

- Alkaline phosphatase < 2.5 x ULN.

- Serum creatinine < 1.5 x ULN.

Exclusion Criteria:

- Chemotherapy within four weeks of first course of PS-341. (Patients may have been on
hormonal therapy).

- Patients who previously received high-dose chemotherapy (higher than the standard
doses of chemotherapy) and/or peripheral blood stem cell transplantation.

- Radiation therapy within four weeks of enrollment (excepting palliative XRT).

- Patients not recovered from toxic effects of previous chemotherapy, radiation
therapy, or antibody therapy.

- Patients with > Grade 2 peripheral neuropathy.

- Surgery within four weeks of study enrollment.

- History of severe hypersensitivity reaction to carboplatin

- Electrocardiographic evidence of acute ischemia or new conduction system

- Myocardial infarction within six months of enrollment.

- Patients with brain metastases or central nervous system disease as evidenced by
clinical symptoms.

- History of other malignancy, except nonmelanoma skin cancer or carcinoma in-situ of
the cervix, unless in complete remission and off all therapy for that disease for a
minimum of 5 years. Chemotherapy given for prior cancers will not exclude patients
from participating in this study.

- Patients with previously documented human immunodeficiency virus (HIV) infection.
HIV-positive patients are excluded from the study based on theoretical concerns
regarding the effect of PS-341 on certain aspects of immune function. NF-KB is a
critical T cell activation protein (including through CD40L/CD 154 stimulation) and
also is involved in cytokine production. Because PS 341 effectively blocks NF-KB and
therefore could reduce or block the ability of T lymphocytes and other immune cells
to fight HIV, PS-341 should not be administered to HIV-positive patients. Additional
experiments in animal models are being conducted to better elucidate the effects of
PS-341 on HIV.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac

- Other serious medical or psychiatric illness that could, in the investigator's
opinion, potentially interfere with the completion of treatment according to this

- Patients who are pregnant, suspected to be pregnant, or breast-feeding.

- Patients with a known hypersensitivity to PS-341, boron, or mannitol.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) of Bortezomib with Carboplatin Chemotherapy

Outcome Time Frame:

Assessed Day 21 of each 28 Day cycle, up to 4 cohorts for a total of 8 cycles

Safety Issue:


Principal Investigator

Pedro T. Ramirez, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2003

Completion Date:

April 2007

Related Keywords:

  • Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
  • Platinum Resistant
  • Taxane Resistant
  • Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
  • Bortezomib
  • PS-341
  • Velcade
  • LDP-341
  • MLN341
  • Carboplatin
  • Paraplatin
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms



University of Texas M. D. Anderson Cancer Center Houston, Texas  77030