Combination Trial of Pimasertib (MSC1936369B) With Temsirolimus

NCT01378377 | Terminated Phase 1 Results

• 1 other identifier: EMR 200066-005
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

MEK inhibitor; Temsirolimus; Neoplasms; Phase I; Pimasertib

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Dose Limiting Toxicities (DLTs)

  DLT was defined as any of the following toxicities graded as per National Cancer Institute (NCI) common terminology criteria for adverse events (NCI CTCAE v4.0) encountered within cycle 1 of treatment at any dose level and judged not to be related to the underlying disease or concomitant medications. A treatment emergent adverse event (TEAE) of potential clinical significance such that further dose escalation would expose subjects to unacceptable risk; any Grade \>=3 non-hematological toxicity except Grade 3 asymptomatic increases in liver function tests, diarrhea, nausea or vomiting with duration \<= 48 hours and alopecia; Grade 4 neutropenia of \>5 days duration or febrile neutropenia of \>1 day duration; Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia; any treatment interruption \>2 weeks due to adverse events; any severe, impairing daily functions or life-threatening, complication or abnormality not defined in NCI-CTCAE that is attributable to the therapy.

  Up to 21 Days (within Cycle 1)

Secondary Outcomes (15)

• Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

  From the start of the trial treatment until data cut-off date (23 February 2012)

• Maximum Plasma Concentration (Cmax) of Pimasertib

  Drug-drug interaction (DDI) cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1

• Maximum Plasma Concentration (Cmax) of Temsirolimus

  DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 8

• Time to Reach Maximum Plasma Concentration (Tmax) of Pimasertib

  DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1

• Time to Reach Maximum Plasma Concentration (Tmax) of Temsirolimus

  DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1

Study Arms (3)

Pimasertib 45 mg+Temsirolimus 12.5 mg

EXPERIMENTAL

Drug: Pimasertib; Drug: Temsirolimus

Pimasertib 45 mg+Temsirolimus 25 mg

EXPERIMENTAL

Drug: Pimasertib; Drug: Temsirolimus

Pimasertib 75 mg+Temsirolimus 25 mg

EXPERIMENTAL

Drug: Pimasertib; Drug: Temsirolimus

Interventions

Pimasertib DRUG

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.

Also known as: MSC1936369B

Pimasertib 45 mg+Temsirolimus 12.5 mg; Pimasertib 45 mg+Temsirolimus 25 mg

Temsirolimus DRUG

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.

Pimasertib 45 mg+Temsirolimus 12.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (3)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Location

For Recruiting Locations in the US contact US Medical Information in

Rockland, Massachusetts, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

Related Publications (2)

• Mita M, Fu S, Piha-Paul SA, Janku F, Mita A, Natale R, Guo W, Zhao C, Kurzrock R, Naing A. Phase I trial of MEK 1/2 inhibitor pimasertib combined with mTOR inhibitor temsirolimus in patients with advanced solid tumors. Invest New Drugs. 2017 Oct;35(5):616-626. doi: 10.1007/s10637-017-0442-3. Epub 2017 Feb 13.

  PMID: 28194539 DERIVED

• Liu X, Lorusso P, Mita M, Piha-Paul S, Hong DS, Fu S, McQuinn L, Asatiani E, Doyle LA, Chen HX, Hess KR, Kurzrock R, Naing A. Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response. Oncologist. 2014 Apr;19(4):426-8. doi: 10.1634/theoncologist.2013-0231. Epub 2014 Mar 25.

  PMID: 24668327 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide; temsirolimus

Limitations and Caveats

No formal efficacy evaluation was performed for this trial due to early termination of the trial.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2011
• First Posted: June 22, 2011
• Study Start: May 27, 2011
• Primary Completion: February 23, 2012
• Study Completion: February 23, 2012
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2017-10

Locations

US (3)