Combination Trial MSC1936369B With Temsirolimus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01378377
Recruitment Status : Completed
First Posted : June 22, 2011
Last Update Posted : June 16, 2014
Information provided by (Responsible Party):
EMD Serono

Brief Summary:
The research trial is testing the experimental drug MSC1936369B (Pimasertib) and the drug TORISEL, given together, in the treatment of advanced solid tumors. The primary purpose of the study is to determine the maximum tolerated dose and the recommended Phase II dose (RP2D) of the drug combination.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: MEK inhibitor MSC1936369B and Temsirolimus Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors
Study Start Date : June 2011
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm Drug: MEK inhibitor MSC1936369B and Temsirolimus

The starting dose of MSC1936369B will be 45mg QD.

The starting dose of Temsirolimus will be 12.5 mg/week

Dosing of MSC1936369B and Temsirolimus will occur in combination: MSC1936369B will be taken orally, QD, on days 1-15 and temsirolimus will be infused IV on days 1, 8 and 15 in successive 21-day cycles. Dose escalation will proceed until Maximum Tolerated Dose (MTD) is reached.

Number of Cycles: The treatment will be continued until disease progression, intolerable toxicity, investigator's decision to discontinue treatment, or withdrawal of consent by the subject.

Other Name: Pimasertib

Primary Outcome Measures :
  1. Number of Dose Limiting Toxicities [ Time Frame: 21 months ]

    DLTs are any of the following toxicities observed within first cycle of treatment and judged not to be related to underlying disease or concomitant medications:

    • Any Grade ≥ 3 non-hematological toxicity with certain exceptions
    • Grade 4 neutropenia of > 5 days or or febrile neutropenia of > 1 day
    • Grade 3 thrombocytopenia with bleeding or grade 4 thrombocytopenia
    • Any treatment interruption > 2 weeks due to AEs not related to the underlying disease or concomitant medication
    • Any severe or life-threatening condition not defined in the NCI-CTCAE that is attributable to the therapy

Secondary Outcome Measures :
  1. Number of participants experiencing any treatment-emergent adverse event [ Time Frame: 21 months ]
  2. Plasma Pharmacokinetic Parameters (Cmax, AUC and T1/2) of MSC1936369B [ Time Frame: 21 months ]
  3. Plasma Pharmacokinetic Parameters (Cmax, AUC and T1/2) of temsirolimus [ Time Frame: 21 months ]
  4. Pharmacodynamic markers (levels of pERK and pS6 levels in PBMCs) [ Time Frame: 21 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subjects with histologically or cytologically confirmed solid tumors, either refractory to standard therapy or for which no effective standard therapy is available.
  2. Measurable or evaluable disease at baseline by RECIST 1.0.
  3. Age ≥ 18 years.
  4. Subject has read and understands the informed consent form and is willing and able to give informed consent.
  5. Performance Status score of ≤ 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
  6. Women of childbearing potential must have a negative blood pregnancy test at the screening visit.
  7. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to screening, during the trial and for 3 months after the last dose of trial medication.

Additional inclusion criteria also apply.

Exclusion Criteria:

  1. The subject has previously been treated with an mTOR inhibitor or a MEK inhibitor and taken off treatment due to drug-related adverse events.
  2. The subject has received any of the following:

    • Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, any investigational agent or any other anti-cancer therapy within 28 days (6 weeks for nitrosoureas or mitomycin C) of Day 1 of trial treatment; non-cytotoxic chemotherapy or investigational agent with limited potential for delayed toxicity is permitted if terminated at least 5 halflives prior to Day 1 of trial treatment.
    • Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation.
  3. The subject has not recovered from toxicity due to prior therapy to baseline or Common Terminology Criteria for Adverse Events (CTCAE v4.0) of Grade 1 or less (except alopecia).
  4. The subject has poor organ or marrow function
  5. History of CNS metastases or primary CNS tumor, unless subject has been previously treated for these conditions, is asymptomatic and has had no requirement for anticonvulsants or high dose corticosteroids for a minimum of 2 weeks prior to entry into the trial.
  6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of Day 1 of trial drug treatment.
  7. Recent major surgery or trauma (within the last 28 days), unhealing/open wounds, diabetic ulcers, recent drainage of significant volume of ascites or pleural effusion.
  8. History of congestive heart failure, unstable angina, myocardial infarction, symptomatic cardiac conduction abnormality, pacemaker, or other clinically significant cardiac disease or history of a stroke within 3 months prior to entering the trial.
  9. Baseline corrected QT interval on screening electrocardiogram (ECG) (QTc) ≥ 460 ms or left ventricular ejection fraction (LVEF) < 40% on screening echocardiogram.
  10. Other uncontrolled intercurrent diseases
  11. Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis or history of retinal vein occlusion, or medically relevant abnormal ophthalmology assessments at screening.
  12. Known or suspected allergy to MSC1936369B, temsirolimus, other rapamycins (sirolimus, everolimus, etc.), their excipients, or any agent given in the course of this trial.
  13. Immunization with attenuated live vaccines within one week of trial entry (examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, etc.).
  14. Concomitant use of any medications or substances that are strong inhibitors or inducers of CYP3A enzyme, including, but not limited to, phenytoin, carbamazepine, barbiturates, azoles, rifampin, phenobarbital, or St. John's Wort.
  15. Pregnant or lactating female.
  16. Legal incapacity or limited legal capacity.

Additional exclusion criteria also apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01378377

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States
United States, Massachusetts
For Recruiting Locations in the US contact US Medical Information in
Rockland, Massachusetts, United States
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Sponsors and Collaborators
EMD Serono
Study Director: Lars Damstrup, MD, PhD, Merck KGaA

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: EMD Serono Identifier: NCT01378377     History of Changes
Other Study ID Numbers: EMR 200066-005
First Posted: June 22, 2011    Key Record Dates
Last Update Posted: June 16, 2014
Last Verified: June 2014

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

Additional relevant MeSH terms:
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents