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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01085331
• Other study ID #: EMR200066_004
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 4, 2010
• Last updated: April 20, 2015
• Start date: March 2010
• Est. completion date: April 2012

Study information

• Verified date: April 2015
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeFrance: Ministry of HealthItaly: Ethics CommitteeItaly: Ministry of HealthSpain: Comité Ético de Investigación ClínicaSpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Belgium	Research Site	Leuven
Italy	Research Site	Napoli
Spain	Research Site	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

Belgium,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 years	Yes
Primary	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		3 years	No
Secondary	Part 1 or Safety Run-in Part: To assess the pharmacokinetics of MSC1936369B and irinotecan		3 years	No
Secondary	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		3 years	No
Secondary	Part 1 or Safety Run-in Part: To explore candidate markers for tumor characteristics and predictive of antitumor activity		3 years	No
Secondary	Part 1 or Safety Run-in Part: To explore circulating markers in serum		3 years	No
Secondary	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		3 years	No
Secondary	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		3 years	No
Secondary	Part 2 or Phase II Randomized part: To explore candidate markers for tumor characteristics and predictive of antitumor activity		3 years	No
Secondary	Part 2 or Phase II Randomized part: To explore circulating markers in serum		3 years	No