Combination Trial of Pimasertib (MSC1936369B) With Temsirolimus

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Temsirolimus; Drug: Pimasertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01378377

EMR 200066-005

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 3 patient groups

Pimasertib 45 mg+Temsirolimus 12.5 mg

Experimental group

Treatment:

Drug: Temsirolimus

Drug: Pimasertib

Drug: Temsirolimus

Drug: Pimasertib

Pimasertib 45 mg+Temsirolimus 25 mg

Experimental group

Treatment:

Drug: Temsirolimus

Drug: Pimasertib

Drug: Temsirolimus

Drug: Pimasertib

Pimasertib 75 mg+Temsirolimus 25 mg

Experimental group

Treatment:

Drug: Temsirolimus

Drug: Pimasertib

Drug: Temsirolimus

Drug: Pimasertib