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

Ovarian Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00964756
• Other study ID #: F080807013 (UAB 0821)
• Secondary ID: 5R01CA090547-02O
• Status: Completed
• Phase: Phase 1
• First received: June 11, 2009
• Last updated: February 11, 2013
• Start date: August 2009
• Est. completion date: April 2012

Study information

• Verified date: February 2013
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: April 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Genetic:
• Ad5.SSTR/TK.RGD
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

Drug:
• Ganciclovir (GCV)
GVC Day 5-18 IV 5 mg/kg BID all groups

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kim KH, Dmitriev I, O'Malley JP, Wang M, Saddekni S, You Z, Preuss MA, Harris RD, Aurigemma R, Siegal GP, Zinn KR, Curiel DT, Alvarez RD. A phase I clinical trial of Ad5.SSTR/TK.RGD, a novel infectivity-enhanced bicistronic adenovirus, in patients with re — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation for toxicity		2 years	Yes
Secondary	Molecular Studies for evaluation of gene transfer and generation of wild type adenovirus, viral shedding and clinical efficacy		30 days	No