MEK Inhibitor MSC1936369B Plus FOLFIRI in Second Line K-Ras Mutated Metastatic Colorectal Cancer (mCRC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01085331
First received: March 4, 2010
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

The research trial is testing the experimental treatment MSC1936369B in combination with FOLFIRI, as second-line treatment in metastatic K Ras mutated colorectal cancer subjects. The study will be run in two parts:

Part 1, or Safety Run-in Part: Will determine the maximum tolerated dose and the recommended Phase II dose (RP2D) of MSC1936369B combined with FOLFIRI as second-line treatment in subjects with metastatic K Ras mutated colorectal cancer.

Part 2 or Phase II Randomised Part: Will assess the anti-tumor activity of MSC1936369B combined with FOLFIRI compared to FOLFIRI with placebo as second-line treatment in metastatic K Ras mutated colorectal cancer subjects.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Mek Inhibitor MSC1936369B
Drug: Placebo
Drug: FOLFIRI
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Comparative, Multicenter, Exploratory, and Placebo-controlled Phase II Trial of FOLFIRI Plus MSC1936369B or Placebo With a Safety run-in Part as Second-line Treatment of Metastatic K Ras Mutated Colorectal Cancer Subjects

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Part 1 or Safety Run-in Part: To determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) of MSC1936369B in combination with FOLFIRI as second-line treatment in subjects with K-Ras mutated metastatic colorectal cancer [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Part 2 or Phase II Randomized part: To assess the anti-tumor activity of MSC1936369B in combination with with FOLFIRI in subjects with K-Ras mutated metastatic colorectal cancer in terms of Progression-Free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 1 or Safety Run-in Part: To assess the pharmacokinetics of MSC1936369B and irinotecan [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 1 or Safety Run-in Part: To explore the anti-tumor activity of MSC1936369B and FOLFIRI in subjects with K-Ras mutated metastatic colorectal cancer [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 1 or Safety Run-in Part: To explore candidate markers for tumor characteristics and predictive of antitumor activity [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 1 or Safety Run-in Part: To explore circulating markers in serum [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 2 or Phase II Randomized part: To determine the safety and tolerability of MSC1936369B and FOLFIRI in subjects with K-Ras mutated metastatic colorectal cancer [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 2 or Phase II Randomized part: To assess the antitumor activity in terms of response rate, clinical benefit, overall survival, and tile to progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 2 or Phase II Randomized part: To explore candidate markers for tumor characteristics and predictive of antitumor activity [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Part 2 or Phase II Randomized part: To explore circulating markers in serum [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2010
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 or Safety Run-in Part: Arm 1 Drug: Mek Inhibitor MSC1936369B

Part 1 or Safety Run-in Part:

Arm 1: Safety Run-in Arm 1 subjects will be dosed with Mek Inhibitor MSC1936369B orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle AND will be dosed with FOLFIRI at conventional doses on days 1 and 15 of the same 28 day cycle.

Other Name: Pimasertib
Experimental: Part 2 or Phase II Randomized part: Arm 1 Drug: Mek Inhibitor MSC1936369B

Part 2 or Phase II Randomized part:

Arm 1: Part II Arm 1 subjects will be randomized to receive Mek Inhibitor MSC1936369B orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle at the recommended Phase II dose AND will be dosed with FOLFIRI at conventional doses on days 1 and 15 of the same 28 day cycle.

Other Name: Pimasertib
Experimental: Part 2 or Phase II Randomized part: Arm 2 Drug: Placebo

Part 2 or Phase II Randomized part:

Arm 2: Part II Arm 2 subjects will be randomized to receive placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle AND will be dosed with FOLFIRI on days 1 and 15 of the same 28 day cycle.

Experimental: Part 2 or Phase II Randomized part Drug: FOLFIRI

Part 2 or Phase II Randomized part:

Arm 2: Part II Arm 2 subjects will be randomized to receive placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle AND will be dosed with FOLFIRI on days 1 and 15 of the same 28 day cycle.


Detailed Description:

Part 1 or Safety Run-in Part: Single Arm Masking: Open Allocation: N/A

Part 2 or Phase II Randomised Part: 2 Arms Masking: Double Blind - Subject is blinded, Caregiver is blinded, Investigator is blinded and Outcomes Assessor is blinded Allocation: Randomized

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

For Safety Run-in and Phase II:

  1. Histologically confirmed K-Ras mutated colon/rectum cancer.
  2. Subject's disease must have progressed during or after a first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy with or without bevacizumab.
  3. Evidence of metastatic measurable disease at trial entry as per Response Evaluation Criteria in Solid Tumors. Complete tumor assessment performed within 14 days prior to first trial drug administration.
  4. Male / female subjects aged greater or equal to 18 years.
  5. Subject has read and understood the Informed Consent Form.
  6. Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Subjects and their partners must be willing to avoid pregnancy during the trial.

Exclusion Criteria:

For Safety Run-in and Phase II:

  1. Bone marrow impairment
  2. Renal impairment
  3. Liver function and liver cell integrity abnormality
  4. History of central nervous system (CNS) metastases
  5. History of difficulty of swallowing, malabsorption or other chronic gastrointestinal disease
  6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than 1.
  7. Known HIV positivity, active hepatitis C, or active hepatitis B.
  8. Has received extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation
  9. Has received chemotherapy, any investigational drug, or having participated in an other clinical trial within the past 4 weeks prior to trial first drug administration.
  10. Has a history of any other significant medical disease
  11. Past or current history (within the last 2 years prior to inclusion) of malignancies except for the indication under this study
  12. Has significant cardiac conduction abnormalities and/or pacemaker.
  13. Is a pregnant or nursing female.
  14. Has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion.
  15. Other significant disease that in the Investigator's opinion would exclude the subject from the trial.
  16. Known hypersensitivity to the trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s).
  17. Legal incapacity or limited legal capacity
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085331

Locations
Belgium
Research Site
Leuven, Belgium
Italy
Research Site
Napoli, Italy
Spain
Research Site
Barcelona, Spain
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Study Director Merck Serono S.A., Geneva
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01085331     History of Changes
Other Study ID Numbers: EMR200066_004
Study First Received: March 4, 2010
Last Updated: October 21, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
France: Ministry of Health
Italy: Ethics Committee
Italy: Ministry of Health
Spain: Comité Ético de Investigación Clínica
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by EMD Serono:
Mek Inhibitor
Metastatic Colorectal Cancer
K-Ras Mutation
Phase II
Second line K-Ras mutated metastatic colorectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 16, 2014