A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission

Study Overview
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Brief Summary
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The study was a Phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial of vismodegib (GDC-0449) in patients with ovarian cancer in a second or third complete remission. Patients were randomized in a 1:1 ratio to either vismodegib or placebo. Randomization was stratified based on whether their cancer was in a second or third complete remission.

Official Title
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A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Vismodegib (GDC-0449) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Vismodegib 150 mg
* Drug: Placebo to vismodegib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma Must be in second or third complete remission, have received chemotherapy (platinum-based and/or non-platinum-based) for recurrent disease, and have achieved a complete remission after their most recent chemotherapy regimen. Complete remission is defined as no symptoms suggestive of persistent cancer, computed tomography (CT) scan of the chest/abdomen/pelvis without evidence of ovarian cancer within 4 weeks of randomization, and normal CA-125 (measured within 2 weeks of randomization) following completion of prior chemotherapy. The study investigator should confirm the status of disease remission by CT scan before patient enrollment. If patient has lymphadenopathy by CT scan and the investigator thinks that it is unlikely due to ovarian cancer, this patient is considered eligible. If indicated, a confirmatory biopsy should be performed. Patients must have completed their most recent cytotoxic chemotherapy regimen (platinum-based or non-platinum based) no less than 3 weeks and no more than 14 weeks prior to randomization. Archival tissue must be available and requested. Negative pregnancy test on Day 1 (first day the patient receives vismodegib or placebo). For women of childbearing potential: Use of two effective methods of contraception, including one barrier method. Exclusion Criteria: Pregnancy or lactation. Patients whose ovarian cancer is in first remission. Patients must not have experienced more than two prior recurrences of disease. Concurrent non-protocol-specified anti-tumor therapy, either approved or unapproved (eg, chemotherapy, hormonal therapy, other targeted therapy, radiation therapy, surgery, herbal therapy). Hormonal replacement therapies for treatment of postmenopausal symptoms do not exclude patients from this study. Current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study while enrolled in this study. History of other malignancies within 3 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately treated basal cell carcinoma (BCC) or squamous-cell carcinoma of the skin; ductal carcinoma in situ of the breast; or carcinoma in situ of the cervix. Uncontrolled medical illnesses such as infection requiring intravenous (IV) antibiotics. Life expectancy < 12 weeks. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vismodegib 150 mg<br>Patients received vismodegib 150 mg orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study. | Drug: Vismodegib 150 mg<br>* Vismodegib 150 mg was provided in hard gelatin capsules.<br>* Other names: GDC-0449;|
| Placebo Comparator: Placebo to vismodegib<br>Patients received placebo to vismodegib orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study. | Drug: Placebo to vismodegib<br>* Placebo to vismodegib consisted of the excipients for vismodegib without the active molecule in hard gelatin capsules matching the active drug product in color and size.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the time between randomization and disease progression, as confirmed by radiography, or death for any reason. Since patients were in remission at the start of the study, they had no evidence of the presence of tumors. Disease progression was defined as radiographic evidence of a tumor. Tumor assessments by computed tomography (CT) of the chest, abdomen, and pelvis were performed at screening and every 8 weeks during the study. | From randomization date through the data cut-off date of May 15, 2010, up to 100 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) in Patients With Versus Without Hedgehog Antigen Tumor Expression | Hedgehog antigen expression was measured with immunohistochemical methods in tumor tissue taken from each patient prior to enrollment in the study. The percentage of cells with (> 0%) and without (0%) Hedgehog antigen expression was measured microscopically. PFS was defined as the time between randomization and disease progression, as confirmed by radiography, or death for any reason. Tumor assessments by computed tomography (CT) of the chest, abdomen, and pelvis were performed at screening and every 8 weeks during the study. | From randomization date through the data cut-off date of May 15, 2010, up to 100 weeks | 
| Overall Survival | Overall survival was defined as the time from randomization until death by any cause. | From randomization date through the data cut-off date of May 15, 2010, up to 100 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Hedgehog, Hedgehog Pathway Inhibitor