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

• Status: Completed
• Trial end date: 2020-11-04
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: AstraZeneca; GlaxoSmithKline
• Treatments: Gefitinib; Topotecan

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
• Patients must have adequate hepatic, renal, and bone marrow function, defined as serum creatinine/=2.0 X the upper limit of normal (ULN); alanine aminotransferase (ALT)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).