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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
AstraZeneca
GlaxoSmithKline
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00317772
First received: April 21, 2006
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.

Condition Intervention Phase
Ovarian Cancer
Peritoneal Neoplasms
Fallopian Tube Cancer
Drug: Topotecan
Drug: Gefitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Weekly Topotecan and Gefitinib (Iressa) in Patients With Platinum-Resistant Ovarian, Peritoneal, of Fallopian Tube Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Dose Limiting Toxicity [ Time Frame: Continual reassessment method, prior to each 28 day cycle ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patient Response + Duration [ Time Frame: Baseline and Monthly Evaulation ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: September 2004
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topotecan + Gefitinib
Topotecan: 2.0, 3.0, or 4.0 mg/m^2 IV Days 1, 8 and 15 of 28 day cycle; Gefitinib: 250 mg by mouth (PO) daily.
Drug: Topotecan
2 mg/m^2 IV Weekly Over 30 Minutes on Days 1, 8, and 15.
Drug: Gefitinib
250 mg by mouth PO daily x 28 Days
Other Name: Iressa

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317772

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
AstraZeneca
GlaxoSmithKline
Investigators
Principal Investigator: Judith Wolf, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00317772     History of Changes
Other Study ID Numbers: 2003-0322
Study First Received: April 21, 2006
Last Updated: October 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Epithelial Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Epidermal Growth Factor
Platinum Hypersensitivity
Hycamtin
Gefitinib
Iressa
Topotecan
EGFR

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Gefitinib
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014