CCR5-blockade in Metastatic Colorectal Cancer (MARACON)
This study is currently recruiting participants.
Verified August 2013 by National Center for Tumor Diseases, Heidelberg
University Hospital Heidelberg
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
First received: October 24, 2012
Last updated: August 20, 2013
Last verified: August 2013
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.
Advanced Stage Colorectal Cancer Patients Standard of Care Chemotherapy
||Observational Model: Case-Only
Time Perspective: Prospective
||Treatment of Advanced Colorectal Cancer Patients With Hepatic Liver Metastases Using the CCR5-Antagonist Maraviroc (Phase I Maracon Trial)
Primary Outcome Measures:
- safety as occurence of adverse events ≥ Grade 3 according to CTCAE, Version 4.0 criteria, that are definitely, probably, or possible related to the administration of the investigational agent [ Time Frame: after eight weeks of treatment ] [ Designated as safety issue: Yes ]
safety, tolerability and feasibility will be assessed after eight weeks of continuous intake of the CCR5-inhibitor. Safety measures include blood analyses (hematologic, liver function, renal function etc.) and the overall performance status of the patient. Especially infections and infection-related events are investigated.
Biospecimen Retention: Samples With DNA
Secondary Outcome Measures:
- Progression Free Survival [ Time Frame: one year after eight weeks of treatment ] [ Designated as safety issue: No ]
Patients will be evaluated for one year afterwards to assess progression free survival.
- Tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: after eight weeks of treatment ] [ Designated as safety issue: No ]
Tumor response will be evaluated after eight weeks of continuous treatment with the CCR5-inhibitor, using the RECIST criteria on MRI images (comparing pre- and post-treatment)
- Tissue level responses of growth inhibition via the CCR5 axis [ Time Frame: during the first four weeks of treatment ] [ Designated as safety issue: No ]
The evaluation of tissue alterations within the tumor microenvironment induced by CCR5-inhibition will be performed during the first four weeks of treatment, comparing the pre-treatment tissue situation with the post-treatment situation.
- Overall survival [ Time Frame: one year after eight weeks of treatment ] [ Designated as safety issue: No ]
Patients will be evaluated for one year afterwards to assess overall survival.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||November 2013 (Final data collection date for primary outcome measure)
CCR5-inhibitor at 300 mg/bid
colorectal cancer patients with liver metastases (twelve patients treated with 300 mg/bid)
Twelve patients with 300 mg/bid
Other Name: Celsentri
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
large university hospital with local private practice referrers
- 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 golermular 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01736813
|National Center for Tumor Diseases, Department of Medical Oncology
|Heidelberg, Baden-Württemberg, Germany, 69120 |
|Contact: Niels Halama, MD +496221563839 ext 7 Niels.Halama@med.uni-heidelberg.de |
|Contact: Dirk Jaeger, MD +49622156722 ext 9 Dirk.Jaeger@nct-heidelberg.de |
|Principal Investigator: Niels Halama, MD |
|Sub-Investigator: Dirk Jaeger, MD |
|Sub-Investigator: Henning Schulze-Bergkamen, MD |
|Sub-Investigator: Martin Haag, MD |
|Sub-Investigator: Christoph Springfeld, MD, PhD |
|Sub-Investigator: Kerstin Lowinski, MD |
National Center for Tumor Diseases, Heidelberg
University Hospital Heidelberg
||Niels Halama, MD
||National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
||Dirk Jaeger, MD
||National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Germany
No publications provided
||National Center for Tumor Diseases, Heidelberg
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 24, 2012
||August 20, 2013
||Germany: Federal Institute for Drugs and Medical Devices
Keywords provided by National Center for Tumor Diseases, Heidelberg:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 06, 2014
Neoplasms, Second Primary
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases