Topotecan and Gefitinib (Iressa) for Ovarian, Peritoneal, or Fallopian Tube Cancer

January 11, 2022 updated by: M.D. Anderson Cancer Center

A Phase I/II Study of Weekly Topotecan and Gefitinib (Iressa) in Patients With Platinum-Resistant Ovarian, Peritoneal, of Fallopian Tube Cancer

The purposes of this study are:

  1. To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) weekly of topotecan in combination with standard dose gefitinib in patients with relapsed, platinum-resistant, ovarian, peritoneal or fallopian tube cancers that are epidermal growth factor receptor (EGF-R) positive (>/= 1+).
  2. To determine the response rate and response duration in this patient population treated with the maximum tolerated dose (MTD) of topotecan administered on a weekly schedule in combination with standard dose gefitinib, given by way of the mouth (PO) daily.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Gefitinib inhibits the activity of a molecule present on the cancer cell that plays a role in cancer cell growth. Topotecan is an FDA approved drug used to treat ovarian cancer that is still present after treatment with chemotherapy. It is also used to treat recurrent ovarian cancer (patients whose cancer returns after they have been cancer-free for a period of time).

Before treatment starts, you will have a complete physical exam, routine blood tests (about 2-3 teaspoons), a chest x-ray, and a CT scan or MRI. Women who are able to have children must have a negative blood pregnancy test.

There are 2 phases to this study. In the first phase, 3 different dose levels of topotecan are being studied. The dose of topotecan that you receive will depend on when you are enrolled. It will also depend on whether or not other participants had side effects from their treatment. Although the dose of topotecan will vary, the dose of gefitinib is the same for all participants. Up to 6 participants may be treated at each dose. The goal of this portion of the study is to find the highest safe dose of this drug combination. Up to 18 patients will be treated on this part of the study.

Once the highest safe dose of topotecan has been found, the second phase of the study will begin. In this phase, all participants will receive the same dose of topotecan and gefitinib. Up to 40 patients will be enrolled in this part of the study (but 6 will be from the 1st portion of the study.

Each treatment cycle is 28 days long. You will take one gefitinib tablet by mouth every day beginning on Day 1. In addition, you will be given topotecan through a catheter (tube) placed in a vein over 30 minutes on Days 1, 8, and 15.

Blood tests to check your kidney, liver, and bone marrow function and a complete checkup (physical examination, including a pelvic and rectal exam) will be done before each course of therapy and a month after treatment ends. About 2-3 teaspoons of blood will be collected for routine blood tests each time blood is drawn during this study. Follow up CT scans or MRI scans will be done after every 2 to 3 cycles to evaluate your response to treatment.

You will be taken off study if your disease gets worse or intolerable side effects occur. If you have a complete response to this therapy (no evidence of cancer) then treatment will continue for an additional 6 months and then stop. All treatment is given on an outpatient basis at UTMDACC.

You will be monitored for at least 30 days after your last dose of therapy. If you have side effects related to this treatment combination, you will be monitored longer (until the side effects have gone away).

This is an investigational study. Both gefitinib and topotecan are FDA approved and commercially available. However, their use together in this study is investigational. A total of up to 52 patients will take part in this study. All will be enrolled at UTMDACC.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women with platinum-resistant, histologically confirmed epithelial ovarian, fallopian tube or peritoneal cancer. Resistance is defined as: Progression of disease during platinum chemotherapy, or progression of disease within 6 months of completing platinum chemotherapy, or failure to achieve a complete response, with persistent macroscopic disease, after an adequate trial of primary therapy.
  • EGF-R expression must be positive (e.g., 1+ or greater) See appendix G.
  • Patients with a known hypersensitivity to platinum compounds, who have failed a desensitization regimen, or in the opinion of the investigator, are not good candidates for desensitization, are eligible.
  • Patients must have measurable disease.
  • Unlimited number of prior chemotherapy regimens are allowed.
  • Zubrod performance status </= 2.
  • Patients must have adequate hepatic, renal, and bone marrow function, defined as serum creatinine </= 2 mg/dl (estimated creatinine clearance 50 ml/min); total bilirubin < /=2.0 X the upper limit of normal (ULN); alanine aminotransferase (ALT) </= 2X ULN; white blood count (WBC) >/= 3,000/mm3; absolute neutrophil count (ANC) >/= 1,500/mm3; platelets >/= 100,000/mm3.
  • At least three weeks must have elapsed from completion of chemotherapy or radiation therapy.
  • At least 30 days must have elapsed from completion of treatment with a non-approved or investigational drug.
  • Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with the policies of the hospital. The only approved consent is appended to this protocol.
  • Women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

Exclusion Criteria:

  • Patients with borderline or low malignant potential tumors are not eligible.
  • Patients who have had prior therapy with topoisomerase I inhibitors.
  • Patients who are pregnant or lactating.
  • Concurrent chemotherapy, radiation therapy, or surgery (excluding palliative radiation).
  • Concurrent, uncontrolled, medical or psychiatric disorders.
  • Patients with an active infection.
  • Patients with a known hypersensitivity to topotecan or iressa.
  • Patients with severe cardiovascular disease (i.e. arrhythmias requiring chronic treatment or congestive heart failure) (NYHA classification III or IV).
  • 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.
  • Patients with overt psychosis or mental disability or otherwise incompetent to give informed consent.
  • Patients who have had prior anti-EGFR therapy (i.e. Tarceva, Cetuximab).
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.
  • Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St. John's Wort.
  • Any evidence of clinically active interstitial lung disease (patient with chronic stable radiographic changes who are asymptomatic are eligible).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Topotecan + Gefitinib

Phase I: Topotecan: 2.0, 3.0, or 4.0 mg/m^2 by vein Days 1, 8 and 15 of 28 day cycle.

Gefitinib: 250 mg by mouth daily.

Phase II: Topotecan starting dose: MTD from Phase I by vein Days 1, 8, and 15 of 28 day cycle.

Gefitinib: 250 by mouth daily for 28 Days.
Drug: Topotecan

Phase I Starting Dose: 2 mg/m^2 by vein Weekly Over 30 Minutes on Days 1, 8, and 15.

Phase II: MTD dose from Phase I by vein weekly on Days 1, 8, and 15.

Drug: Gefitinib

Phase I: 250 mg by mouth daily for 28 Days.

Phase II: 250 mg by mouth daily for 28 Days.

Other Names:
  • Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicity (DLT)
Time Frame: Continual reassessment method, prior to each 28 day cycle, an average of 60 days
Dose-limiting toxicity defined as any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity. The DLT (dose-limiting toxicity) is defined as any Grade 4 hematological toxicity and any > Grade 3 non-hematologic toxicity.
Continual reassessment method, prior to each 28 day cycle, an average of 60 days
Maximum Tolerated Dose (MTD) of Topotecan
Time Frame: At end of first course, prior to each new course (28 day cycle). Continual reassessment method (CRM) during each course for toxicity, an average of 60 days
Maximum tolerated dose is highest dose level in which 6 patients treated with at most 1 experiencing DLT.
At end of first course, prior to each new course (28 day cycle). Continual reassessment method (CRM) during each course for toxicity, an average of 60 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 61 weeks
Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension. Complete Response (CR): disappearance of all target and non-target lesions and no evidence of new lesions. Partial Response (PR): At least 30% decrease in sum of longest dimensions (LD) of all target measurable lesions. Increasing Disease: At least a 20% increase in sum of LD of target lesions taking as reference smallest sum LD or appearance of new lesions within 8 weeks of study entry. Progression on existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin. Death due to disease without prior objective documentation of progression. Global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression.
61 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

GlaxoSmithKline
AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 2, 2004

Primary Completion (ACTUAL)

November 4, 2020

Study Completion (ACTUAL)

November 4, 2020

Study Registration Dates

First Submitted

April 21, 2006

First Submitted That Met QC Criteria

April 21, 2006

First Posted (ESTIMATE)

April 25, 2006

Study Record Updates

Last Update Posted (ACTUAL)

February 7, 2022

Last Update Submitted That Met QC Criteria

January 11, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2003-0322

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Peritoneal Neoplasms

Clinical Trials on Topotecan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe