Study to Evaluate the Safety, Tolerability and Efficacy of FOLFOX + CT-011 Versus FOLFOX Alone

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: CT-011; Drug: FOLFOX

• Registration Number: NCT00890305
• Lead Sponsor: Medivation, Inc.

Brief Summary

This clinical trial will be performed in previously untreated patients with metastatic colorectal cancer. The study will evaluate the safety, tolerability and efficacy of the study drug, CT-011, in combination with FOLFOX chemotherapy (FOLFOX4 or mFOLFOX6) compared with treatment by FOLFOX alone.

Detailed Description

The proposed clinical trial will be a multi-center, randomized, open label, active control study in previously untreated patients with metastatic colorectal cancer aimed to evaluate the safety, tolerability and efficacy of the monoclonal antibody, CT-011, administered at 3mg/kg in combination with FOLFOX chemotherapy (FOLFOX4 or mFOLFOX6) compared with treatment by FOLFOX alone. Approximately 168 patients are planned to be enrolled to this study.

Study Timeline

• Study First Submitted: 2009-04-28
• Study First Submitted QC: 2009-04-28
• Study First Posted: 2009-04-29
• Study Start: 2009-05
• Primary Completion: 2012-05
• Study Completion: 2013-03
• Status Verified: 2015-06
• Disposition First Submitted: 2015-06-10
• Disposition First Submitted QC: 2015-06-10
• Last Update Submitted: 2015-06-10
• Disposition First Posted: 2015-07-08
• Last Update Posted: 2015-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

1. Patient's age is 18 years or older, both genders.
2. Patients with metastatic disease who are eligible for first line FOLFOX chemotherapy. Adjuvant or neoadjuvant given at least 12 months prior for non-metastatic disease is permitted.
3. ECOG performance status ≤ 1
4. At least 4 weeks from prior major surgery or radiotherapy.
5. Life expectancy >3 months
6. Hematology: ANC ≥ 1.5X109/L; Platelets >100x109/L.
7. Adequate Renal function
8. Adequate Hepatic functions
9. Normal Cardiac function

Exclusion Criteria

1. Patients who had adjuvant or neoadjuvant therapy for non-metastatic disease given within the last 12 months.
2. Patients who had received Oxaliplatin within 12 months prior to diagnosis of metastatic disease.
3. Patients on concurrent anti cancer therapy other than that allowed in the study.
4. Patients on concurrent steroids, other than those allowed for routine antiemetics, or inhaled steroids
5. Presence of clinically apparent or suspected brain metastasis.
6. Patients who have had myocardial infarction, severe congestive heart failure, or significant arrhythmia within the past 6 months.
7. Serious active infection at the time of pre-study screening.
8. Active or history of autoimmune disorders/conditions.
9. Women who are pregnant or lactating
10. Concurrent active malignancy.
11. Ascites, pleural effusions, or osteoblastic bone metastases as the only site of disease.
12. Other prior malignancies, except for cured or adequately treated malignancies for which there has been no evidence of activity for more than 5 years.
13. Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study.
14. Patients with history of life threatening allergic reactions to food or drugs
15. Patients with symptomatic peripheral neuropathy> Grade 1.
16. Known positive HIV, Hepatitis B surface antigen or Hepatitis C antibody.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CT-011 in combination with FOLFOX	CT-011	CT-011 (3 mg/kg) administered intravenously every 4 weeks for 4 weeks and every 12 weeks thereafter until disease progression or maximum tolerance. FOLFOX (FOLFOX4 or mFOLFOX6) administered 7 days after the first administration of CT-011 and repeated every 14 days for up to 24 cycles. At the end of FOLFOX therapy, patients who have not progressed will be eligible for maintenance chemotherapy with 5-FU/leucovorin at the same dose and schedule until disease progression or study drug discontinuation.
CT-011 in combination with FOLFOX	FOLFOX	CT-011 (3 mg/kg) administered intravenously every 4 weeks for 4 weeks and every 12 weeks thereafter until disease progression or maximum tolerance. FOLFOX (FOLFOX4 or mFOLFOX6) administered 7 days after the first administration of CT-011 and repeated every 14 days for up to 24 cycles. At the end of FOLFOX therapy, patients who have not progressed will be eligible for maintenance chemotherapy with 5-FU/leucovorin at the same dose and schedule until disease progression or study drug discontinuation.
FOLFOX	FOLFOX	FOLFOX (FOLFOX-4 or mFOLFOX6) administered every 14 days for up to 24 cycles. At the end of FOLFOX therapy, patients who have not progressed will be eligible for maintenance chemotherapy with 5-FU/leucovorin at the same dose and schedule until disease progression or study drug discontinuation.

Primary Outcome Measures

Name	Time	Method
The primary endpoint will be the median progression free survival in patients treated with CT-011 plus FOLFOX compared to that of patients treated with FOLFOX alone.	32 months

Secondary Outcome Measures

Name	Time	Method
Composite of safety, tolerability, pharmacokinetics and immunogenicity of CT-011.	32 months
Anti tumor activity of the antibody.	32 months
Objective response rate by RECIST.	32 months
Progression-free survival rates.	32 months
Response duration.	32 months
Overall survival.	32 months
Tumor and immunological markers.	32 months

Trial Locations

Locations (31)

The Cancer Center of Huntsville, PC; 🇺🇸 Huntsville, Alabama, United States

InterDistrict Dispensary of Oncology Diseases with Stationary; 🇧🇬 Varna, Bulgaria

InterDistrict Dispensary in Oncology Diseases with Stationary; 🇧🇬 Shumen, Bulgaria

InterDistrict Dispensary in Oncology Diseases with Stationary-Ruse, EOOD; 🇧🇬 Ruse, Bulgaria

MHAT "Dr. Tota Venkova"; 🇧🇬 Gabrovo, Bulgaria

Specialized Hospital for Active Treatment for Oncology; 🇧🇬 Sofia, Bulgaria

Signal Point Clinical Research Center; 🇺🇸 Middletown, Ohio, United States

Multiprofile Hospital for Active Treatment "Sv. Marina", EAD,; 🇧🇬 Varna, Bulgaria

Multiprofile Hospital for Active Treatment "Tsaritza Joanna"; 🇧🇬 Sofia, Bulgaria

Joe Arrington Cancer Research and Treatment Center; 🇺🇸 Lubbock, Texas, United States

Clinical Emergency Hospital - Oncology Department; 🇷🇴 Constanta, Romania

Oncolab SRL, No. 1; 🇷🇴 Craiova, Romania

Center of Medical Oncology; 🇷🇴 Iasi, Romania

Clinical Hospital Pelican Oradea; 🇷🇴 Oradea, Romania

Fundacion de Investigacion de Diego; 🇵🇷 Santurce, Puerto Rico

Cancer Clinic; 🇮🇳 Nagpur, Maharashtra, India

Curie Manavata Cancer Centre, Opp.; 🇮🇳 Nashik, Maharashtra, India

"Prof. Dr. Ion Chiricuţă" Institute of Oncology; 🇷🇴 Cluj-Napoca, Romania

Clinic of Oncology - Radiotherapy; 🇷🇴 Tg. Mures, Romania

G. Kuppuswamy Naidu Memorial Hospital; 🇮🇳 Pappanaickenpalayam, Coimbatore, Tamilnadu, India

Ponce School of Medicine/CAIMED Center; 🇵🇷 Ponce, Puerto Rico

Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences; 🇮🇳 Sheikhpura, Patna, Bihar, India

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Hospital Regional nivel III Cayetano Heredia Essalud Piura; 🇵🇪 Piura, Peru

No. 1 City Hospital; 🇷🇴 Ploiesti, Romania

"Sf. Ioan cel Nou" Clinical Emergency County Hospital; 🇷🇴 Suceava, Romania

Deenanath Mangeshkar Hospital and Research Centre; 🇮🇳 Pune, Maharashtra, India

Hospital Almanzor Aguinaga Asenjo - Chiclayo; 🇵🇪 Chiclayo, Peru

Clinica Ricardo Palma; 🇵🇪 Lima, Peru

University of South Florida; 🇺🇸 Tampa, Florida, United States

Ruby Hall Clinic; 🇮🇳 Pune, Maharashtra, India