Advanced Solid TumorPhase 1NCT01378377
Combination Trial of Pimasertib (MSC1936369B) With Temsirolimus
A Phase 1 study testing Pimasertib and Temsirolimus in people with Advanced Solid Tumor, run by EMD Serono at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- Pimasertib and Temsirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- 27 May 2011to 23 Feb 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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 locations and contacts
3 sites in 1 country.
United States3 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas
Cedars-Sinai Medical Center
Los Angeles, California
For Recruiting Locations in the US contact US Medical Information in
Rockland, Massachusetts
About this study
Official title: Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors
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
- Being tested
- Pimasertib, Temsirolimus
- Keywords
- MEK inhibitor, Temsirolimus, Neoplasms, Phase I, Pimasertib
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimasertibDrug
Also called MSC1936369B
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.
PimasertibDrug
Also called MSC1936369B
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.
TemsirolimusDrug
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.
TemsirolimusDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pimasertib 45 mg+Temsirolimus 12.5 mg | Experimental | Not described Receives: Drug: Pimasertib; Drug: Temsirolimus |
| Pimasertib 45 mg+Temsirolimus 25 mg | Experimental | Not described Receives: Drug: Pimasertib; Drug: Temsirolimus |
| Pimasertib 75 mg+Temsirolimus 25 mg | Experimental | Not described Receives: Drug: Pimasertib; Drug: Temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 21 Days (within Cycle 1)
Secondary outcomes (15)
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. The TEAEs were those events that occur between first dose of trial treatment and up to 30 days after last dose of the trial treatment that were absent before treatment or that worsened relative to pretreatment state.
Measured: From the start of the trial treatment until data cut-off date (23 February 2012)
Maximum Plasma Concentration (Cmax) of Pimasertib
Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: 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
Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: 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
Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: 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
Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Area Under the Concentration Time Curve During a Dosing Interval (AUCtau) and Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib
The AUCtau was defined as the area under the concentration curve divided by the dosing interval. AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1 for AUCtau; DDI cohorts: Day 1 of Cycle 1 AUC0-inf
Area Under Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Temsirolimus
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Terminal Half-life (t1/2) of Pimasertib
The t1/2 was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Terminal Half-life (t1/2) of Temsirolimus
The t1/2 was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Clearance From Plasma Following Oral Administration (CL/f) of Pimasertib
Clearance (CL) of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. The CL obtained after oral dose (CL/F) was influenced by the fraction of the dose absorbed (bioavailability). Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Total Body Clearance From Plasma Following Intravenous Administration (CL) of Temsirolimus
The clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Volume of Distribution (Vz/F) of Pimasertib
Volume of distribution (Vz) was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The Vz after oral dose (Vz/F) was influenced by the fraction absorbed. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Volume of Distribution (Vz) of Temsirolimus
The Vz was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Pharmacokinetic parameters were reported based on DDI and non-DDI cohorts as per plan.
Measured: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Number of Subjects With Disease Control Rate
Disease control is defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) >=12 weeks), based on tumor assessments as determined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. CR: The disappearance of all lesions and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline. SD: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since treatment started.
Measured: From the start of the trial treatment until data cut-off date (23 February 2012)
Phospho Extracellular Signal Regulated Kinase (pERK ) Levels and Phospho Ribosomal Protein S6 (pS6) Levels in in Peripheral Blood Mononuclear Cells (PBMCs)
During the first cycle (either Cycle 1 non-DDI or Cycle 1-DDI) blood samples will be collected for pharmacodynamic marker assessments by flow cytometry such as phospho-ERK and phospho- S6 activities in PBMCs
Measured: DDI cohorts: Days 1, 9 and 10 of Cycle 1; Non-DDI cohorts: Days 1, 8 and 9 of Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study start27 May 2011
- Primary completion23 Feb 2012
- Study completion23 Feb 2012
Why it stopped: The trial was stopped due to the toxicities observed with the combination of pimasertib and temsirolimus.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378377
- Sponsor's protocol ID
- EMR 200066-005
- Status last verified
- Oct 2017
- First submitted
- 20 Jun 2011
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28194539Liu 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.
PubMed 24668327
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Trial of MEK1/2 Inhibitor MSC1936369B Combined With Temsirolimus in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01378377
- Acronym / sponsor ID
- EMR 200066-005
- Conditions
- Advanced Solid Tumor
- Keywords
- MEK inhibitor, Temsirolimus, Neoplasms, Phase I, Pimasertib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was stopped due to the toxicities observed with the combination of pimasertib and temsirolimus.
- Enrolment
- 33 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- 27 May 2011 (actual)
- Primary completion
- 23 Feb 2012 (actual)
- Study completion
- 23 Feb 2012 (actual)
- First posted
- 22 Jun 2011 (estimated)
- Results
- Posted 30 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PimasertibAlso: MSC1936369BPimasertib 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. | Drug | Pimasertib 45 mg+Temsirolimus 12.5 mg, Pimasertib 45 mg+Temsirolimus 25 mg |
| PimasertibAlso: MSC1936369BPimasertib 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. | Drug | Pimasertib 75 mg+Temsirolimus 25 mg |
| TemsirolimusTemsirolimus 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. | Drug | Pimasertib 45 mg+Temsirolimus 12.5 mg |
| TemsirolimusTemsirolimus 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. | Drug | Pimasertib 45 mg+Temsirolimus 25 mg, Pimasertib 75 mg+Temsirolimus 25 mg |
Primary outcome
Number of Subjects With Dose Limiting Toxicities (DLTs)
Time frame: Up to 21 Days (within Cycle 1)
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.
15 secondary outcomes
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time frame: From the start of the trial treatment until data cut-off date (23 February 2012)
Maximum Plasma Concentration (Cmax) of Pimasertib
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Area Under the Concentration Time Curve During a Dosing Interval (AUCtau) and Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib
Time frame: DDI cohorts: Days 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1 for AUCtau; DDI cohorts: Day 1 of Cycle 1 AUC0-inf
Area Under Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Temsirolimus
Time frame: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Terminal Half-life (t1/2) of Pimasertib
Time frame: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Terminal Half-life (t1/2) of Temsirolimus
Time frame: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Clearance From Plasma Following Oral Administration (CL/f) of Pimasertib
Time frame: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Total Body Clearance From Plasma Following Intravenous Administration (CL) of Temsirolimus
Time frame: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Apparent Volume of Distribution (Vz/F) of Pimasertib
Time frame: DDI cohorts: Days 1 and 9 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Volume of Distribution (Vz) of Temsirolimus
Time frame: DDI cohorts: Days 9 and 16 of Cycle 1; Non-DDI cohorts: Day 8 of Cycle 1
Number of Subjects With Disease Control Rate
Time frame: From the start of the trial treatment until data cut-off date (23 February 2012)
Phospho Extracellular Signal Regulated Kinase (pERK ) Levels and Phospho Ribosomal Protein S6 (pS6) Levels in in Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: DDI cohorts: Days 1, 9 and 10 of Cycle 1; Non-DDI cohorts: Days 1, 8 and 9 of Cycle 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28194539Mita 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.
- Derived from this study: PubMed 24668327Liu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono, an affiliate of MerckKGaA, Darmstadt, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pimasertib and Temsirolimus in people with Advanced Solid Tumor, run by EMD Serono at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Dose Limiting Toxicities (DLTs) (time frame: Up to 21 Days (within Cycle 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01378377, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2018.