A Study of the Safety and Efficacy of CNTO 888 in Combination With SoC (Standard of Care) Chemotherapy in Patients With Solid Tumors

An Open-label, Multicenter, Phase 1b Study of CNTO 888 (an Anti-CCL 2 Monoclonal Antibody) in Combination With Chemotherapies for the Treatment of Subjects With Solid Tumors

The purpose of this study is to evaluate the safety and dose regimen of CNTO 888 when administered to patients with solid tumors in combination with 4 standard of care chemotherapy regimens.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: CNTO888 + docetaxel; Drug: CNTO888 + gemcitabine; Drug: CNTO888 + Paclitaxel and carboplatin; Drug: CNTO888+DOXIL®/ Caelyx® doxorubicin HCl liposome injection

Detailed Description

CNTO 888 is an antibody that works by blocking a protein called CC-chemokine ligand 2 (CCL2). In research studies CCL2, has been shown to increase the growth of new blood vessels which help the tumor to survive. It is hoped that blocking CCL2 may help to control tumor growth.

Patients will receive one of four treatments. A dose of 15 mg/kg CNTO 888 will be administered once every 3 weeks in combination with either docetaxel, gemcitabine, or paclitaxel-carboplatin in Treatment Arms 1, 2, and 3, respectively; and 10 mg/kg CNTO 888 will be administered once every 2 weeks with DOXIL® / Caelyx® (doxorubicin HCl liposome injection) for intravenous infusion once every 4 weeks in Treatment Arm 4. The maximum time that patients will be in the study is one year.

Safety assessments will be conducted throughout the course of the study. Safety assessments include the monitoring of side effects,clinical laboratory tests (hematology, biochemistry, and urinalysis), vital signs, and physical examinations. CNTO 888 will be administered IV at 2 different doses (15 mg/kg or 10 mg/kg) dependant on the chemotherapy combination. Combination therapy will be continued until disease progression, unacceptable toxicity, the patient refuses further combination therapy, withdraws consent, or is treated for 1 year

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Sanchinarro, Spain
• United States
  • Michigan
    • Detroit, Michigan, United States
  • Washington
    • Tacoma, Washington, United States

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:

• Documentation of an advanced solid tumor
• No more than 2 previous anticancer therapies
• good performance status
• adequate bone marrow, liver, and renal function / adequate blood test values
• willing to use birth control measures

Exclusion Criteria:

• No residual toxicities resulting from previous therapy
• no known allergies, hypersensitivity, or intolerance to antibodies or chemotherapies
• clinically significant bleeding or requiring concurrent therapeutic dose of anticoagulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; CNTO888 + docetaxel 15 mg/kg CNTO 888 every 3 weeks plus docetaxel 75 mg/m2 every 3 weeks	Drug: CNTO888 + docetaxel; 15 mg/kg CNTO 888 every 3 weeks plus docetaxel 75 mg/m2 every 3 weeks
Experimental: 2; CNTO888 + gemcitabine 15 mg/kg CNTO 888 every 3 weeks plus gemcitabine 1000 mg/m2 administered on Days 1 and 8 of the 3-week cycle	Drug: CNTO888 + gemcitabine; 15 mg/kg CNTO 888 every 3 weeks plus gemcitabine 1000 mg/m2 administered on Days 1 and 8 of the 3-week cycle
Experimental: 3; CNTO888 + Paclitaxel and carboplatin 15 mg/kg CNTO 888 every 3 weeks plus paclitaxel 175 mg/m2 and carboplatin dosed to AUC 6 every 3 weeks	Drug: CNTO888 + Paclitaxel and carboplatin; 15 mg/kg CNTO 888 every 3 weeks plus paclitaxel 175 mg/m2 and carboplatin dosed to AUC 6 every 3 weeks
Experimental: 4; CNTO888+DOXIL®/ Caelyx® doxorubicin HCl liposome injection 10 mg/kg CNTO 888 every 2 weeks plus DOXIL®/Caelyx® (doxorubicin HCl liposome injection) 50 mg/m2 every 4 weeks	Drug: CNTO888+DOXIL®/ Caelyx® doxorubicin HCl liposome injection; 10 mg/kg CNTO 888 every 2 weeks plus DOXIL®/Caelyx® (doxorubicin HCl liposome injection) 50 mg/m2 every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of the study is to evaluate the safety of CNTO 888 when administered to patients with solid tumors in combination with 4 standard of care chemotherapy regimens.	During treatment and up to 30 days after last study treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics(rate of movement in the body and then the clearance)	during study as specified in the protocol (interim analysis) and at End of Study (1 year)
Pharmacodynamics (action of drug on body systems)	during study as specified in the protocol (interim analysis) and at End of Study (1 year)

Collaborators and Investigators

• Sponsor: Centocor, Inc.

Publications and helpful links

General Publications

• Brana I, Calles A, LoRusso PM, Yee LK, Puchalski TA, Seetharam S, Zhong B, de Boer CJ, Tabernero J, Calvo E. Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol. 2015 Mar;10(1):111-23. doi: 10.1007/s11523-014-0320-2. Epub 2014 Jun 15.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: September 16, 2010
• First Submitted That Met QC Criteria: September 16, 2010
• First Posted (Estimate): September 20, 2010

Study Record Updates

• Last Update Posted (Estimate): May 30, 2012
• Last Update Submitted That Met QC Criteria: May 29, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: chemotherapy; monoclonal antibody; solid tumor; standard of care
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Docetaxel; Carboplatin; Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CR016462; 2009-015541-23 (EudraCT Number); CNTO888STM1002 (Other Identifier: Centocor)