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

Phase II Study to Evaluate the Safety, Tolerability and Efficacy of FOLFOX + CT-011 Versus FOLFOX Alone Administered Intravenously to Patients With Colorectal Adenocarcinoma Previously Untreated for Metastatic Disease

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: CT-011; Drug: FOLFOX

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 Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Gabrovo, Bulgaria
    • MHAT "Dr. Tota Venkova"
  • Ruse, Bulgaria
    • InterDistrict Dispensary in Oncology Diseases with Stationary-Ruse, EOOD
  • Shumen, Bulgaria
    • InterDistrict Dispensary in Oncology Diseases with Stationary
  • Sofia, Bulgaria
    • Multiprofile Hospital for Active Treatment "Tsaritza Joanna"
  • Sofia, Bulgaria
    • Specialized Hospital for Active Treatment for Oncology
  • Varna, Bulgaria
    • InterDistrict Dispensary of Oncology Diseases with Stationary
  • Varna, Bulgaria
    • Multiprofile Hospital for Active Treatment "Sv. Marina", EAD,
• India
  • Bihar
    • Sheikhpura, Patna, Bihar, India, 800 014
      • Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Cancer Clinic
    • Nashik, Maharashtra, India, 422004
      • Curie Manavata Cancer Centre, Opp.
    • Pune, Maharashtra, India, 411001
      • Ruby Hall Clinic
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital and Research Centre
  • Tamilnadu
    • Pappanaickenpalayam, Coimbatore, Tamilnadu, India, 641037
      • G. Kuppuswamy Naidu Memorial Hospital
• Peru
  • Chiclayo, Peru
    • Hospital Almanzor Aguinaga Asenjo - Chiclayo
  • Lima, Peru
    • Clinica Ricardo Palma
  • Piura, Peru
    • Hospital Regional nivel III Cayetano Heredia Essalud Piura
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine/CAIMED Center
  • Santurce, Puerto Rico, 00909
    • Fundacion de Investigacion de Diego
• Romania
  • Cluj-Napoca, Romania, 400015
    • "Prof. Dr. Ion Chiricuta" Institute of Oncology
  • Constanta, Romania, 900591
    • Clinical Emergency Hospital - Oncology Department
  • Craiova, Romania, 200535
    • Oncolab SRL, No. 1
  • Iasi, Romania
    • Center of Medical Oncology
  • Oradea, Romania, 410469
    • Clinical Hospital Pelican Oradea
  • Ploiesti, Romania
    • No. 1 City Hospital
  • Suceava, Romania
    • "Sf. Ioan cel Nou" Clinical Emergency County Hospital
  • Tg. Mures, Romania, 540141
    • Clinic of Oncology - Radiotherapy
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • The Cancer Center of Huntsville, PC
  • Florida
    • Tampa, Florida, United States, 33606
      • University Of South Florida
  • New York
    • New York, New York, United States, 10017
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • Texas
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT-011 in combination with 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.	Drug: CT-011; Drug: FOLFOX; FOLFOX-4: each cycle consists of the following: oxaliplatin 85 mg/m2 on Day 1, leucovorin 200 mg/m2/day on Day 1 and Day 2 followed by 5-FU 400 mg/m2 bolus and a 22 hour infusion of 5-FU 600 mg/m2 for two consecutive days. mFOLFOX-6: each cycle consists of the following: oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 on Day 1, followed by 5-FU 400 mg/m2 bolus, followed by 5-FU 1200 mg/m2/day for two consecutive days (total 2,400 mg/m2 over 46-48 hours).
Active Comparator: 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.	Drug: FOLFOX; FOLFOX-4: each cycle consists of the following: oxaliplatin 85 mg/m2 on Day 1, leucovorin 200 mg/m2/day on Day 1 and Day 2 followed by 5-FU 400 mg/m2 bolus and a 22 hour infusion of 5-FU 600 mg/m2 for two consecutive days. mFOLFOX-6: each cycle consists of the following: oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 on Day 1, followed by 5-FU 400 mg/m2 bolus, followed by 5-FU 1200 mg/m2/day for two consecutive days (total 2,400 mg/m2 over 46-48 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Medivation, Inc.
• Investigators: Principal Investigator: Leonard B Saltz, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 28, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Metastatic colorectal cancer; FOLFOX chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pidilizumab
• Other Study ID Numbers: CT-2008-01; 2009-014593-18 (EudraCT Number)