Combination Trial of Pimasertib (MSC1936369B) With Temsirolimus
Condition: Advanced Solid Tumor
Intervention: Pimasertib; Pimasertib; Temsirolimus; Temsirolimus
Intervention description: Pimasertib will be administered in fasted state at a dose of 45 mg once daily orally on Days 1 to 15. Treatment will be continued until disease progression, intolerable toxicity, investigator's decision to discontinue treatment, or withdrawal of consent.; Pimasertib will be administered in fasted state at a dose of 75 mg once daily orally on Days 1 to 15. Treatment will be continued until disease progression, intolerable toxicity, investigator's decision to discontinue treatment, or withdrawal of consent.; Temsirolimus will be administered at a dose of 12.5 mg as intravenous infusion over a 30-60 minute period once a week within 10 minutes after administration of pimasertib on Days 1, 8 and 15 in successive 21-day cycles. Treatment will be continued until disease progression, intolerable toxicity, investigator's decision to discontinue treatment, or withdrawal of consent.; Temsirolimus will be administered at a dose of 25 mg as intravenous infusion over a 30-60 minute period once a week within 10 minutes after administration of pimasertib on Days 1, 8 and 15 in successive 21-day cycles. Treatment will be continued until disease progression, intolerable toxicity, investigator's decision to discontinue treatment, or withdrawal of consent.
Intervention MeSH terms: Niacinamide; Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MEK inhibitor; Temsirolimus; Neoplasms; Phase I; Pimasertib

Summary:

      The research trial is testing the experimental drug 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 (MTD) and the recommended Phase 2 dose (RP2D) of the
      drug combination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with histologically or cytologically confirmed solid tumors, either
             refractory to standard therapy or for which no effective standard therapy is
             available.

          -  Measurable or evaluable disease at baseline by RECIST 1.0.

          -  Age >= 18 years.

          -  Subject has read and understands the informed consent form and is willing and able to
             give informed consent.

          -  Performance Status score of less than or equal to (<=) 1 according to the Eastern
             Cooperative Oncology Group (ECOG) scale.

          -  Women of childbearing potential must have a negative blood pregnancy test at the
             screening visit.

          -  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:

          -  The subject has previously been treated with mammalian target of rapamycin (mTOR)
             inhibitor or a mitogen-activated protein kinase (MEK) inhibitor and taken off
             treatment due to drug-related AEs.

          -  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 half-lives 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.

          -  The subject has not recovered from toxicity due to prior therapy to baseline or CTCAE
             v4.0 of Grade 1 or less (except alopecia).

          -  The subject has poor organ or marrow function as defined in protocol.

          -  History of central nervous system (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.

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months of Day 1 of trial drug treatment.

          -  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.

          -  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.

          -  Baseline corrected QT interval on screening electrocardiogram (ECG) (QTc) >= 460 ms or
             left ventricular ejection fraction (LVEF) < 40% on screening echocardiogram.

          -  Other uncontrolled intercurrent diseases

          -  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.

          -  Known or suspected allergy to pimasertib, temsirolimus, other rapamycins (sirolimus,
             everolimus, etc.), their excipients, or any agent given in the course of this trial.

          -  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.).

          -  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.

          -  Pregnant or lactating female.

          -  Legal incapacity or limited legal capacity.

        Additional exclusion criteria also apply.