Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Patients received vismodegib 150 mg orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study.

Patients received placebo to vismodegib orally once daily until radiographically confirmed disease progression, intolerable toxicity, or withdrawal from the study.

Vismodegib 150 mg was provided in hard gelatin capsules.

Vismodegib 150 mg

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.

Placebo to vismodegib

Josina Reddy, M.D., Ph.D.

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.

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

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

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.

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.

Overall survival was defined as the time from randomization until death by any cause.

Genentech, Inc.

Adverse events were reported for the safety-evaluable population, which was defined as all patients who received at least one dose of study treatment.

Placebo to Vismodegib

Total

Age, Continuous

Sex: Female, Male

Medical Communications

Intent-to-treat patient population: All randomized patients.

Progression-free Survival (PFS)

0% of cells with hedgehog punctate stain

> 0% of cells with Hedgehog punctate stain

Intent-to-treat patient population: All randomized patients. Tissue for evaluation was only available for 29 patients in the vismodegib group and 28 patients in the placebo group.

Progression-free Survival (PFS) in Patients With Versus Without Hedgehog Antigen Tumor Expression

Overall Survival

Overall Study

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Bevacizumab

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Folic Acid

Calcium, Dietary

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients received vismodegib 150 mg orally once daily starting on Day 3 of each 2-week treatment cycle. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient.

Patients received placebo to vismodegib orally once daily starting on Day 3 of each 2-week treatment. In addition, patients received either Modified FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) + bevacizumab or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) + bevacizumab on Days 1-3 of each 2-week treatment cycle. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient.

Vismodegib 150 mg was provided in hard gelatin capsules in 3 different strengths, 25 mg, 125 mg, and 150 mg.

Bevacizumab 5 mg/kg was administered intravenously (IV) over 90 minutes for the first infusion, shortening to 60 and 30 minutes for subsequent infusions.

Following administration of bevacizumab, patients received oxaliplatin 85 mg/m\^2 IV administered over 90 minutes concurrently with folinic acid 400 mg/m\^2 (d,I-racemic form, or 200 mg/m\^2 I-isomer form) IV administered over 120 minutes, then fluorouracil 400 mg/m\^2 administered as an IV bolus, then 2400 mg/m\^2 administered as a continuous IV infusion over 46 hours.

Modified FOLFOX

Following administration of bevacizumab, patients received irinotecan 180 mg/m\^2 IV administered over 90 minutes concurrently with folinic acid 400 mg/m\^2 (d,I-racemic form, or 200 mg/m\^2 I-isomer form) administered IV over 120 minutes, then fluorouracil 400 mg/m\^2 administered as an IV bolus, then fluorouracil 2400 mg/m\^2 administered as a continuous IV infusion over 46 hours.

FOLFIRI

Jennifer Low, M.D., Ph.D.

This was a randomized, placebo-controlled, double-blind study of vismodegib (GDC-0449) added to biochemotherapy standard-of-care regimens for metastatic colorectal cancer (CRC), with treatment until disease progression. Patients received either FOLFOX (FOL=leucovorin calcium \[folinic acid\], F=fluorouracil, OX=oxaliplatin) or FOLFIRI (FOL=leucovorin calcium \[folinic acid\] F=fluorouracil, IRI=irinotecan hydrochloride) chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use was made by the treating physician and patient. Patients were randomized to receive vismodegib or placebo and were stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease was present at baseline.

A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer

A Randomized, Placebo-Controlled Phase II Study of Vismodegib (GDC-0449, Systemic Hedgehog Antagonist) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer

Progression-free survival (PFS) was defined as the time from randomization to the earlier of documented disease progression (PD) or death from any cause. PD: At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. For patients without measurable disease, PD was defined as an increase in the size of a lesion to one that is measurable or unequivocal progression of a non-target lesion.

Indian + Sonic Hedgehog antigen expression was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from archival tumor tissue taken from each patient prior to enrollment in the study. Results are reported in 3 categories; the 33% of patients with the lowest level of expression, the 35% of patients with a middle level of expression, and the 32% of patients with the highest level of expression. PFS was defined as the time between randomization and disease progression, as confirmed by radiography, or death for any reason.

Adverse events were reported for the safety-evaluable population, which was defined as all patients who received at least one dose of investigational drug treatment.

Placebo will be administered beginning on Cycle 1, Day 3 once daily by oral dosing. For Cycles 2 and beyond, placebo will be administered once daily beginning on Day 1.

Placebo With FOLFOX+Bevacizumab

GDC-0449 (150 mg) will be administered beginning on Cycle 1, Day 3 once daily by oral dosing. For Cycles 2 and beyond, GDC-0449 will be administered once daily beginning on Day 1.

Vismodegib (GDC-0449) With FOLFOX+Bevacizumab

Placebo With FOLFIRI+Bevacizumab

Vismodegib (GDC-0449) With FOLFIRI+Bevacizumab

≤ 33%, n=(16,30)

33% - 67%, n=(18,28)

> 67%, n=(30,17)

Intent-to-treat patient population: All randomized patients. Tissue for evaluation was only available for 64 patients in the vismodegib group and 75 patients in the placebo group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) As Maintenance Therapy in Patients With Ovarian Cancer in a Second or Third Complete Remission	NCT00739661	Ovarian Cancer	Vismodegib 150 ... Placebo to vism...	18 Years -	Genentech, Inc.
A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer	NCT00636610	Metastatic Colo...	Vismodegib 150 ... Placebo to vism... Bevacizumab Modified FOLFOX FOLFIRI	18 Years -	Genentech, Inc.
A Study of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) With Concurrent Chemotherapy and Bevacizumab As First-Line Therapy for Metastatic Colorectal Cancer	NCT00636610	Metastatic Colo...	Vismodegib 150 ... Placebo to vism... Bevacizumab Modified FOLFOX FOLFIRI	18 Years -	Genentech, Inc.

Spots Global Cancer Trial Database for placebo to vismodegib