CCR5-blockade in Metastatic Colorectal Cancer

NCT ID: NCT01736813

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 12 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2014-09-30

Brief Summary

The surface molecule CCR5 is found on tumor cells within liver metastases of colorectal cancer. Inhibition of this molecule leads to a reduction in growth signals for tumor cells and subsequent slowed or halted tumor growth. The agent for the inhibition of CCR5 has already received FDA approval for treatment of HIV and has shown little side effects and toxicities even on long term treatment. Therefore CCR5-inhibition has the potential of providing non-toxic tumor growth inhibition.

Conditions

Colorectal Cancer; Neoplasm Metastasis; Liver Metastases

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

CCR5-inhibitor at 300 mg/bid

colorectal cancer patients with liver metastases (twelve patients treated with 300 mg/bid)

Maraviroc

Intervention Type: DRUG

Twelve patients with 300 mg/bid

Interventions

Maraviroc

Twelve patients with 300 mg/bid

Intervention Type: DRUG

Other Intervention Names

Celsentri

Eligibility Criteria

Inclusion Criteria

• written informed consent (must be available before enrollment in the trial)
• age ≥ 18 years
• male or female patient with a history of treated metastatic stage IV colorectal cancer with liver metastases of the primary colorectal cancer
• histologically confirmed liver metastasis of colorectal cancer with histologically confirmed CCR5 (C-C chemokine receptor type 5) expression in the tumor cells
• expected survival of at least three months
• Karnofsky performance status > 70 %
• patients that have received current standard treatment options (progression or intolerance to oxaliplatin, irinotecan and 5-Fluorouracil with or without treatment combinations of cetuximab and/or bevacizumab or panitumumab)
• no chemotherapy treatment within the last three weeks
• within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified (or as deemed acceptable by trial investigator): absolute neutrophil count (ANC) ≥ 1000/mm3 (≥ 1.0 x 109/L), platelets ≥ 80.000/mm3 (≥ 80 x 109/L), creatinine Clearance limit as assessed by glomerular filtration rate > 60 mL/min/1.73m², ALT (alanine transaminase), AST (aspartate transaminase), and total bilirubin all ≤ 5.0 x ULN (upper limit normal)
• able and willing to give valid written informed consent and to understand character and individual consequences of the clinical trial
• if the patient is female, she must be of non-childbearing potential, or practice adequate contraception.

Exclusion Criteria

• Patients with severe kidney disorders (GFR of <30 mL/min/1.73m² and diagnosed kidney disease) or who are on hemodialysis. The patient requires concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents. Topical or inhalational steroids are permitted.
• Patients taking immunomodulatory medication (Type 1 interferons).
• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment
• Patients with single metastatic lesions (intent to resect the metastasis)
• Patients with metastatic colorectal cancer that have a drastic clinical progression (e.g. from Karnofsky performance 100% to 60%) within the last six weeks before screening cannot participate
• The patient has a history of autoimmune disease.
• The patient has a family history of congenital or hereditary immunodeficiency.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV).or has another confirmed or suspected immunosuppressive or immunodeficient condition.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
• The patient has concurrent chronic severe medical problems (heart failure, uncontrolled diabetes, bleeding disorder etc.), unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• The patient has previous or concomitant malignancies at other sites, except effectively treated carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
• For female patients: the patient is pregnant or lactating.
• Women of childbearing potential: Refusal or inability to use effective means of contraception
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
• Participation in other clinical trials or observation period of competing trials, respectively
• No subject will be allowed to enroll in this trial more than once.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

National Center for Tumor Diseases, Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Niels Halama, MD

Role: PRINCIPAL_INVESTIGATOR

National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany

Dirk Jaeger, MD

Role: STUDY_DIRECTOR

National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Germany

Locations

National Center for Tumor Diseases, Department of Medical Oncology

Heidelberg, Baden-Wurttemberg, Germany

Countries

Germany

References

Halama N, Zoernig I, Berthel A, Kahlert C, Klupp F, Suarez-Carmona M, Suetterlin T, Brand K, Krauss J, Lasitschka F, Lerchl T, Luckner-Minden C, Ulrich A, Koch M, Weitz J, Schneider M, Buechler MW, Zitvogel L, Herrmann T, Benner A, Kunz C, Luecke S, Springfeld C, Grabe N, Falk CS, Jaeger D. Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients. Cancer Cell. 2016 Apr 11;29(4):587-601. doi: 10.1016/j.ccell.2016.03.005.

Reference Type: RESULT

PMID: 27070705 (View on PubMed)

Other Identifiers

2012-000861-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MARACON-001

Identifier Type: -

Identifier Source: org_study_id