Pemetrexed and Gemcitabine for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

Study Overview
=================
Brief Summary
-----------------
This study aims to investigate the efficacy and safety of the combination of pemetrexed and gemcitabine in heavily pre-treated, chemotherapy resistant colorectal cancer patients with KRAS mutations.

Official Title
-----------------
Phase II Study of Pemetrexed and Gemcitabine for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Pemetrexed
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically verified adenocarcinoma in colon or rectum Age >18 Metastatic colorectal cancer progressed after chemotherapy regimens containing fluoropyrimidines, oxaliplatin and irinotecan. KRAS mutation in primary tumour or metastasis. Measurable disease according to RECIST ECOG performance status 0, 1 or 2 Adequate function of liver, kidneys and bone marrow measured by biochemistry (max. 2 weeks before enrolment) EDTA clearance: Uncorrected GFR > 45 ml/min. Neutrophilocytes ≥1.5 x 10^9/l, leukocytes ≥3.0 x 10^9/l, thrombocytes ≥100x10^9/l ALAT ≤ 3 x upper normal value (ULN), bilirubin ≤ 3 x upper normal value, Aptt and INR normal (or 2-3 at AC treatment). (ALAT and basic phosphatase ≤ 5 x upper normal value in case of liver metastases). Blood samples and paraffin embedded tissue from primary tumour and/or metastases for translational research. Fertile men and women (women <2 year after last menstruation) must use efficient birth control. Signed informed consent. Exclusion Criteria: Clinically significant other concurrent disease making the patient unfit for participation in the study according to the investigator. Other malignant disease within 5 years prior to study enrolment, except from planocellular and basal cell carcinomas in the skin or carcinoma-in-situ cervix. Other experimental treatment within 30 days prior to treatment start. Pregnant or breastfeeding women. Clinical or radiological signs of CNS metastases. Planned radiation of target lesions. Concurrent vaccination against yellow fever.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br> | Drug: Pemetrexed<br>* 400 mg/m2 on day 1 of a 3 weeks cycle<br>Drug: Gemcitabine<br>* 1000 mg/m2 intravenously on day 1 and 8 of a 3 weeks cycle<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Assessed every 3 weeks by CT and/or MR scan and evaluated according to RECIST 1.1. Up to 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | Every 3 months until progression or death. Up to 12 months. | 
| Overall survival |  | 12 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal cancer, Metastatic colorectal cancer, Treatment resistant, Chemotherapy refractory, KRAS mutation