MSC2015103B in Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01453387
First received: September 9, 2011
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

The main purpose of this study is to test the experimental drug, MSC2015103B at different dose levels and on different treatment schedules, to see whether it is safe and can be tolerated when given to subjects once a day one day per week over a 21-day period or once a day three times per week over a 21-day period. The investigators would also like to find out how MSC2015103B is broken down by the body.

Additional purposes of the trial are to assess side effects of MSC2015103B and to find out whether MSC2015103B has anti-cancer effects. In addition, the investigators would like to explore pharmacokinetics.


Condition Intervention Phase
Advanced Solid Tumor
Drug: MSC2015103B
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose-Escalation First-In-Human Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral MEK Inhibitor MSC2015103B Administered With Two Different Treatment Schedules in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Proportion of subjects experiencing dose-limiting toxicities (DLT), evaluated over the first cycle of treatment by using the National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0. [ Time Frame: 20 months ] [ Designated as safety issue: Yes ]
  • Number of subjects experiencing dose-limiting toxicities (DLT), evaluated over the first cycle of treatment by using the National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0. [ Time Frame: 20 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of subjects experiencing any treatment emergent adverse event. [ Time Frame: 20 months ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters (AUC) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods. [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters (Cmax) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods. [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters (tmax) of MSC2015103B measured in plasma will be calculated for each cohort using non-compartmental methods. [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • At the end of the trial MSC2015103B pharmacokinetics (AUC) will be calculated using non-compartmental methods [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Proportion of subjects experiencing clinically significant changes in a laboratory parameter and /or vital signs judged to be related to the trial medication [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Proportion of subjects with overall response as defined by confirmed Complete Response (CR) or Partial Response (PR) (using RECIST v1.0) during treatment [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Proportion of subjects with clinical benefit as defined by confirmed CR, PR or Stable Disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • ERK phosphorylation levels will be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation. [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Number of subjects experiencing clinically significant changes in a laboratory parameter and /or vital signs judged to be related to the trial medication [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Number of subjects experiencing any treatment emergent adverse event. [ Time Frame: 20 months ] [ Designated as safety issue: Yes ]
  • Number of subjects with overall response as defined by confirmed Complete Response (CR) or Partial Response (PR) (using RECIST v1.0) during treatment [ Time Frame: 20 months ] [ Designated as safety issue: No ]
  • Number of subjects with clinical benefit as defined by confirmed CR, PR or Stable Disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment [ Time Frame: 20 months ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: September 2011
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 - MSC2015103B (Schedule 1 & 2) Drug: MSC2015103B

Once weekly administration schedule: Days 1, 8, and 15 of a 21-day cycle (Schedule 1) dosing will begin at 150 mcg

Three times weekly administration schedule: Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle (Schedule 2) dosing will begin at 150 mcg

Experimental: Part 2 - MSC2015103B Drug: MSC2015103B
An Expansion Cohort at the MTD or any other suitable dose level may be utilized to further characterize the safety profile and pharmacodynamics of the drug.

  Eligibility

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

Inclusion Criteria:

  1. Pathologically confirmed solid tumor preferably, but not exclusively, including pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma, or melanoma which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available.
  2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤ 1.
  3. Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of and willing to comply with all trial visits and assessments.
  4. Evidence of measurable disease at trial entry as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0.
  5. Willing to provide archival tissue samples for molecular analysis.

Other inclusion criteria also apply.

Exclusion Criteria:

  1. Bone marrow impairment as evidenced by hemoglobin < 9.0 g/dL, neutrophil count < 1.5 x 10^9/L, and/or platelets < 100 x 10^9/L.
  2. Renal impairment as evidenced by serum creatinine > 1.5 x ULN (upper limit of normal) and/or calculated creatinine clearance < 50 mL/min (Cockcroft-Gault formula).
  3. Liver function and liver cell integrity abnormality as defined by total bilirubin> 1.5 x ULN, or aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN. Subjects with albumin < 2.5 g/dL are also excluded.
  4. History of central nervous system (CNS) metastases..
  5. History of difficulty of swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
  6. Chronic diarrhea that is ≥ Grade 2 in severity
  7. Clinically significant cardiac conduction abnormalities.
  8. A left ventricular ejection fraction of < 45%.
  9. A history of stroke or myocardial infarction within the past year.
  10. A history of uveitis and scleritis.
  11. Retinal pathology beyond normal age-related processes.
  12. Evidence of a retinal vein occlusion on fluorescein angiogram or a history of retinal vein occlusion.

    Subjects are also excluded if their ophthalmologist finds that their optic disc is at risk for a central retinal vein occlusion.

  13. History of glaucoma.
  14. Subjects requiring daily and/or chronic systemic steroids.
  15. Pregnant or nursing females.

Other exclusion criteria also apply.

  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: NCT01453387

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Medical Responsible Merck Serono, a division of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01453387     History of Changes
Other Study ID Numbers: EMR 200064-001
Study First Received: September 9, 2011
Last Updated: September 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
MEK inhibitor
Solid Tumor
Phase I

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014