A Study of an Infectivity Enhanced Suicide Gene Expressing Adenovirus for Ovarian Cancer in Patients With Recurrent Ovarian and Other Selected Gynecologic Cancers

Study Overview
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Brief Summary
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In spite of surgical and chemotherapeutic advances, long term survival for advanced and recurrent gynecologic cancers remains dismal and no curative treatment for recurrent disease exists. Novel treatment strategies are needed. This is a study to determine the maximally tolerated dose of and toxicities associated with intraperitoneal delivery of an infectivity enhanced adenovirus that expresses a suicide gene and an gene that allows imaging of gene transfer. This vector will be given in combination with intravenous ganciclovir in patients with recurrent ovarian and other gynecological cancers.

Official Title
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A Phase I Study of AD5.SSTR/TK.RGD; A Tropism Modified Adenovirus Vector for Intraperitoneal Delivery of Therapeutic Genes and Additional Capability of Noninvasive Imaging of Gene Transfer in Patients With Recurrent Ovarian and Other Selected Gynecologic Cancers (Infectivity Enhanced Adenoviral Vectors for Ovarian CA)

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Genetic: Ad5.SSTR/TK.RGD
* Drug: Ganciclovir (GCV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically documented invasive epithelial ovarian, extraovarian, fallopian tube or endometrial carcinoma. Patients must have persistent or recurrent disease after standard debulking/staging surgery and conventional therapy. Patients must have evidence of intraabdominal disease; disease may be measurable or nonmeasurable. Patients must have a GOG performance status of 0, 1, or 2, and have a life expectancy of greater than 3 months. Patients must have adequate hematologic, renal, and hepatic function defined as: WBC > 3,000 ul Granulocytes > 1,500 ul Platelets > 100,000 Creatinine clearance > 80 mg/dl or serum creatinine > 2.0 Serum transaminases < 2.5 x upper limits of normal Normal serum bilirubin PT/PTT/INR < 1.5 x institutional ULN O2 saturation > or = 92 % Patients must be 19 years or older and must have signed informed consent Exclusion Criteria: Patients with epithelial tumors of low malignant potential, stromal tumors and germ cell tumors of the ovary are ineligible to participate in the study. Patients with the only site of disease located beyond the abdominal cavity are ineligible to participate in the study. Patients who are pregnant or lactating are ineligible to participate in the study. Patients with a GOG performance status of 3 or 4 are ineligible to participate in the study. Patients with active heart disease (characterized by angina, unstable arrhythmia, congestive heart failure or EF < 55%, pulmonary hyper- tension, active or chronic debilitating pulmonary disease(i.e., active pneumonia, severe COPD, pulmonary edema, O2 saturation < 92%), or coagulation disorders (i.e. bleeding disorders, or on therapeutic anti- coagulants)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gene therapy<br> | Genetic: Ad5.SSTR/TK.RGD<br>* Group 1 Day 1-3 IP 1 x 10 9th vp/d Group 2 Day 1-3 IP 5 x 10 10th vp/d Group 3 Day 1-3 IP 1 x 10 12th vp/d<br>Drug: Ganciclovir (GCV)<br>* GVC Day 5-18 IV 5 mg/kg BID all groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation for toxicity |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular Studies for evaluation of gene transfer and generation of wild type adenovirus, viral shedding and clinical efficacy |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, Recurrent ovarian cancer and other gynecologic cancers