Study Chairman: Ralph S Freedman, MD, PhD
Study Sponsor: Immunex/MDACC
Research Nurse: Jody K Folloder, BSN

This study is being conducted through the Department of Gynecologic Oncology

Study Schedule

This is a two-arm pilot study of Flt-3 ligand. 16 patients will be randomized to arm A (8 pts) or arm B (8 pts) and treated as follows:

Arm A
Cycle 1: Flt-3 ligand 25mcg/kg subcutaneously per day x 5 days (M to F) x 2 wks
Cycle 2: Flt-3 ligand 25mcg/kg intraperitoneal per day x 5 days (M to F) x 2 wks

Arm B
Cycle 1: Flt-3 ligand 25mcg/kg intraperitoneal per day QD x 5 days (M to F) x 2 wks
Cycle 2: Flt-3 ligand 25mcg/kg subcutaneously per day x 5 days (M to F) x 2 wks

After 2 cycles of treatment (8 weeks), patients will be assessed for tumor response by tumor markers and CT scan. If the disease is at least stable then two more cycles of treatment will be delivered by the same sequence. Patients with no evidence of disease (by CT scan and no rise in tumor markers may be assessed by laparoscopy).

Study Rationale (excerpted from the protocol abstract)

Peritoneal carcinomatosis associated with Müllerian and gastrointestinal tract cancers are causes of significant morbidity and mortality. Intraperitoneal bioimmunotherapy has immunopharmacokinetic advantages and has shown responses in a number of trials with different bioimmunotherapy agents.

Flt-3 ligand is a novel hematopoietic growth factor that has been shown to have antitumor activity in preclinical studies. In normal subjects and in patients with various malignancies, Flt-3 ligand has been shown to induce significant increases in the numbers and in the maturation qualities of dendritic cells in peripheral blood without serious side effects. The doses from 10 to 100 mcg/kg are efficient at inducing DC that have normal functions. The DC enhancing effect plateaued after 9 days of subcutaneous administration. There is no human experience with IP Flt-3 ligand. We have shown that DC obtained from the peritoneal cavity and peripheral blood of patients with peritoneal carcinomatosis have cell surface antigen characteristics of immature antigen presenting cells.

Therefore, we propose to study the effects of Flt-3 Ligand in patients with peritoneal carcinomatosis. In particular, we wish to evaluate whether Flt-3 Ligand when administered by S.C. and IP route, enhances the numbers and maturation of DC in the peritoneal cavity. Since DC appear to be a most important population of antigen presenting cells, an increase in the number and maturation of DC may facilitate activation of tumor associated lymphocytes in the peritoneal cavity. These types of studies may contribute to the development of more effective immunotherapy for these tumors.

Patient Eligibility

Patients with diagnosis of Mullerian carcinoma, (epithelial ovarian or peritoneal carcinoma) or gastrointestinal cancer with abdominal carcinomatosis.
Patients must have at least a clinical, radiologic, or surgical evidence of evaluable disease.
Patients with GI cancer should have received adequate course of prior treatment and should have intact primary unless at risk for obstruction/bleeding.
Patients should be at least 3 weeks from abdominal surgery, 2 weeks from laparoscopy, 3 weeks from chemotherapy, 6 weeks from nitrosoureas, and 3 months from radiation treatment.
Patients must be at least 18 years old and have adequate blood counts and chemistries. Female patients must practice adequate contraception.

Exclusion:

Patients with very bulky abdominal disease cannot be accepted (lesions > 10 cm). Patients w/ symptomatic and bulky liver metastases (> 2 cm) cannot be accepted.

Patients with brain metastases or significant pleural effusions can not be accepted.

Patients with inadequate blood counts, severe weight loss, significant heart disease, or who are pregnant or lactating can not be accepted.

Patients who have had radiation to the entire abdomen can not be accepted.

Patients with active ulcer disease or a history of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis and autoimmune disease)