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

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.

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).