Neoplasms

All Conditions

Rare Diseases

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Intestinal Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Folic Acid

Folfirinox

Folinic Acid

Folate

Vitamin B9

One treatment every 14 days :

* Irinotecan 180mg/m² as a 2-hour IV infusion
* Oxaliplatin 85 mg/m² as a 2-hour IV infusion
* Folinic acid 400 mg/m² as 2-hour IV infusion, in Y with oxaliplatin
* 5-FU 2400 mg/m² as a continuous IV infusion over 46 hours

modified FOLFORINOX

One treatment every 14 days:

* Oxaliplatin 85 mg/m by IV infusion over 2 hours
* Folinic acid: 400 mg/m² or 200 mg/m² if laevorotatory form by IV infusion over 2 hours, in Y with oxaliplatin
* 5FU bolus: 400 mg/m² per 10-minute IV infusion
* 5 FU continuous 2400 mg/m² by IV infusion over 46 hours

Modified FOLFOX

Thomas APARICIO

Sylvain MANFREDI

Randomized, non-comparative, open-label, multi-centre Phase II study to evaluate modified FOLFIRINOX and modified FOLFOX in the locally advenced or metastatic small bowel adenocarcinoma.

The primary objective is to assess the percentage of patients alive without prograssion at 8 months.

Trial Evaluating Modified FOLFIRINOX and Modified FOLFOX in the Treatment of Locally Advanced or Metastatic Small Bowel Adenocarcinoma

Randomized Phase II Trial Evaluating Modified FOLFIRINOX and Modified FOLFOX in the Treatment of Locally Advanced or Metastatic Small Bowel Adenocarcinoma

Centre Hospitalier Universitaire Dijon

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Bone Density Conservation Agents

Bevacizumab

Calcium

Calcium, Dietary

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

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.

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

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.

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.

Genentech, Inc.

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

Placebo to Vismodegib

Total

Age, Continuous

Sex: Female, Male

Medical Communications

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

Progression-free Survival (PFS)

≤ 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
Trial Evaluating Modified FOLFIRINOX and Modified FOLFOX in the Treatment of Locally Advanced or Metastatic Small Bowel Adenocarcinoma	NCT06278545	Locally Advance...	modified FOLFOR... Modified FOLFOX	18 Years -	Centre Hospitalier Universitaire Dijon
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.

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