Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT01390818

Last Updated: 2017-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-04-30

Brief Summary

This research trial is testing a combination of two experimental drugs, MSC1936369B (Mitogen-activated protein extracellular signal-regulated kinase (MEK) Inhibitor) and SAR245409 (Phosphatidylinositol 3-kinase (Pi3K)/Mammalian Target of Rapamycin (mTOR) inhibitor), in the treatment of locally advanced or metastatic solid tumors. The primary purpose of the study is to determine the maximum tolerated dose of the drug combination.

Conditions

Locally Advanced Solid Tumor; Metastatic Solid Tumor; Breast Cancer; Non Small Cell Lung Cancer; Melanoma; Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSC1936369B and SAR245409 once daily

Group Type: EXPERIMENTAL

MSC1936369B (pimasertib)

Intervention Type: DRUG

MSC1936369B (pimasertib) single dose capsule was administered at dose of 15 milligram (mg), 30 mg, 60 mg, 90 mg orally in successive 21-day cycles.Dose escalation was proceeded until Maximum Tolerated Dose (MTD) was reached. Once the MTD was reached, enrollment began in four disease-specific expansion cohorts at either the MTD or a lower dose recommended by the Safety Monitoring Committee. The four expansion cohorts enrolled subjects with Breast Cancer, Non-Small Cell Lung Cancer (NSCLC), Melanoma, and Colorectal Cancer.

SAR245409 (PI3K and mTOR inhibitor)

Intervention Type: DRUG

SAR245409 (PI3K and mTOR inhibitor) capsule was administered orally at a dose of 30 mg, 50 mg, 70 mg and 90 mg in successive 21-day cycles. Dose escalation was proceeded until MTD was reached. Once the MTD was reached, enrollment began in four disease-specific expansion cohorts at either the MTD or a lower dose recommended by the Safety Monitoring Committee. The four expansion cohort enrolled subjects with Breast Cancer, NSCLC, Melanoma, and Colorectal Cancer.

MSC1936369B and SAR245409 twice daily

Group Type: EXPERIMENTAL

MSC1936369B (pimasertib)

Intervention Type: DRUG

MSC1936369B (pimasertib) capsule was administered twice daily orally at a dose of 60 mg and 45 mg in successive 21-day cycles. Dose escalation proceeded until MTD was reached. The maximum tolerated dose of MSC1936369B (pimasertib) was combined with a lower dose of SAR245409 (PI3K and mTOR inhibitor).

SAR245409 (PI3K and mTOR inhibitor)

Intervention Type: DRUG

SAR245409 (PI3K and mTOR inhibitor) was administered twice daily orally at a dose of 30 mg and 50 mg in successive 21-day cycles. Dose escalation proceeded until MTD was reached. The maximum tolerated dose of SAR245409 (PI3K and mTOR inhibitor) was combined with a lower dose of MSC1936369B (pimasertib).

Interventions

MSC1936369B (pimasertib)

MSC1936369B (pimasertib) single dose capsule was administered at dose of 15 milligram (mg), 30 mg, 60 mg, 90 mg orally in successive 21-day cycles.Dose escalation was proceeded until Maximum Tolerated Dose (MTD) was reached. Once the MTD was reached, enrollment began in four disease-specific expansion cohorts at either the MTD or a lower dose recommended by the Safety Monitoring Committee. The four expansion cohorts enrolled subjects with Breast Cancer, Non-Small Cell Lung Cancer (NSCLC), Melanoma, and Colorectal Cancer.

Intervention Type: DRUG

SAR245409 (PI3K and mTOR inhibitor)

SAR245409 (PI3K and mTOR inhibitor) capsule was administered orally at a dose of 30 mg, 50 mg, 70 mg and 90 mg in successive 21-day cycles. Dose escalation was proceeded until MTD was reached. Once the MTD was reached, enrollment began in four disease-specific expansion cohorts at either the MTD or a lower dose recommended by the Safety Monitoring Committee. The four expansion cohort enrolled subjects with Breast Cancer, NSCLC, Melanoma, and Colorectal Cancer.

Intervention Type: DRUG

MSC1936369B (pimasertib)

MSC1936369B (pimasertib) capsule was administered twice daily orally at a dose of 60 mg and 45 mg in successive 21-day cycles. Dose escalation proceeded until MTD was reached. The maximum tolerated dose of MSC1936369B (pimasertib) was combined with a lower dose of SAR245409 (PI3K and mTOR inhibitor).

Intervention Type: DRUG

SAR245409 (PI3K and mTOR inhibitor)

SAR245409 (PI3K and mTOR inhibitor) was administered twice daily orally at a dose of 30 mg and 50 mg in successive 21-day cycles. Dose escalation proceeded until MTD was reached. The maximum tolerated dose of SAR245409 (PI3K and mTOR inhibitor) was combined with a lower dose of MSC1936369B (pimasertib).

Intervention Type: DRUG

Other Intervention Names

Pimasertib; PI3K and mTOR inhibitor; pimasertib; PI3K and mTOR inhibitor

Eligibility Criteria

Inclusion Criteria

• Subject with advanced solid tumors for which there is no approved therapy:

• Advanced solid tumor with diagnosed alteration in one or more of the following genes (PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2, MET, RET, c-KIT, GNAQ, GNA11 and/or
• A histologically or cytologically confirmed diagnosis of one of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma
• Subject with archived tumor tissue available for transfer to the Sponsor
• Subject enrolled at lower dose level cohorts and MTD expansion cohorts must have tumor available for biopsy and agree to pre-treatment and on-treatment tumor biopsies
• Subject has measurable or evaluable disease by response evaluation criteria in solid tumors (RECIST) v1.1
• Subject is aged greater than or equal to (>=) 18 years

Exclusion Criteria

• Relapsed or refractory Kirsten rat sarcoma viral oncogene homolog (KRAS) or neuroblastoma RAS viral oncogene homolog (NRAS) mutated metastatic non-small cell lung cancer (NSCLC) with no approved therapies, or
• Relapsed or refractory metastatic triple negative breast cancer defined as estrogen, progesterone and HER2 negative carcinoma of the breast with no approved therapies, or
• Relapsed or refractory metastatic colorectal cancer (CRC) with dual KRAS and PIK3CA mutation with no approved therapies, or
• BRAF V600E/K mutated unresectable or metastatic melanoma after progression on B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors

• Subject has been previously treated with a PI3K inhibitor or a MEK inhibitor and taken off treatment due to treatment related adverse events
• Subject has received:
• Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anti-cancer therapy within 28 days of trial drug treatment
• Any investigational agent within 28 days of trial drug treatment
• Extensive prior radiotherapy on more than 30% bone marrow reserves, or prior bone marrow/stem cell transplantation
• Subject has not recovered from toxicity due to prior therapy
• Subject has poor organ and marrow function as defined in the protocol
• Subject has a history of central nervous system metastases, unless subject has been previously treated for CNS metastases
• Subject has a history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease
• Subject has a history of recent major surgery or trauma within the last 28 days.
• Subject has participated in another clinical trial within the past 30 days

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 82 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono, a business of Merck KGaA, Darmstadt, Germany

Locations

Pinnacle Oncology Hematology

Scottsdale, Arizona, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Cancer Therapy and Research Center

San Antonio, Texas, United States

Merck Serono Research Site

Milan, , Italy

Merck Serono Research Site

Madrid, , Spain

Countries

United States; Italy; Spain

Other Identifiers

EMR 200066-006

Identifier Type: -

Identifier Source: org_study_id