Pancreatic AdenocarcinomaPhase 1/2NCT01016483
Trial of Gemcitabine With or Without MSC1936369B in Pancreatic Cancer
A Phase 1/2 study testing Pimasertib and Gemcitabine in people with Pancreatic Adenocarcinoma, run by EMD Serono at 2 sites in 2 countries.
Trial summary
The research trial is testing the experimental treatment MSC1936369B in combination with Gemcitabine, in subjects with metastatic pancreatic adenocarcinoma. The study will be run in two parts: Safety Run-In: Will determine the Maximum Tolerated Dose (MTD) and the recommended Phase II dose of MSC1936369B, when combined… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Adenocarcinoma
- What is being tested?
- Pimasertib and Gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 30 Nov 2009to 30 Apr 2015
- Phase
- Phase 1/2
- 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
- Subject has provided signed informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments.
- Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas and availability of tumor sample.
- Evidence of disease (not necessarily measurable disease). Complete tumor assessment including chest X ray, CT scan of abdomen and other scans as necessary to document all sites of disease performed within 28 days prior to trial entry/randomization.
- Age ≥ 18 years.
- Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential is defined as: "All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive."
- 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 and four weeks after the last dose of trial medication. Adequate contraception is defined as two barrier methods, or one barrier method with a spermicide, or intrauterine device. The use of hormonal contraceptives should be avoided in female subjects of childbearing potential due to a possible drug-drug interaction.
Who cannot join
- Bone marrow impairment as evidenced by hemoglobin less (<) 9.0 gram per deciliter (g/dL), neutrophil count < 1.5 x 10^9/ liter (L), platelets < 100 x 10^9/L.
- Renal impairment as evidenced by serum creatinine > 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance < 60 mL/min.
- Liver function abnormality as defined by total bilirubin > 1.5 x ULN, or aspartate aminotransferase/ alanine aminotransferase (AST/ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN.
- Serum calcium > 1 x ULN.
- History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases, is stable by CT scan without evidence of cerebral edema, and has no requirements for corticosteroids or anticonvulsants.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than 1.
- Significant cardiac conduction abnormalities, including QT interval corrected for heart rate (QTc) prolongation of > 480 milliseconds (ms) and/or pacemaker.
- Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis or history of retinal vein occlusion.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
For Recruiting Locations in the United States, please Contact U.S. Medical Information
Rockland, Massachusetts
Germany1 site
For Recruiting Locations outside the United States, Please contact the Merck KGaA Communication Center
Darmstadt
About this study
Official title: Phase II Randomized Trial of MEK Inhibitor MSC1936369B or Placebo Combined With Gemcitabine in Metastatic Pancreas Cancer Subjects
The research trial is testing the experimental treatment MSC1936369B in combination with Gemcitabine, in subjects with metastatic pancreatic adenocarcinoma. The study will be run in two parts:
Safety Run-In: Will determine the Maximum Tolerated Dose (MTD) and the recommended Phase II dose of MSC1936369B, when combined with gemcitabine, in subjects with metastatic pancreatic adenocarcinoma.
Phase II: Will assess the anti-tumor activity of MSC1936369B combined with gemcitabine compared to gemcitabine alone as first line treatment in subjects with metastatic pancreatic adenocarcinoma.
- Conditions
- Pancreatic Adenocarcinoma
- Being tested
- Pimasertib, Gemcitabine, Placebo
- Keywords
- MEK inhibitor, cancer, pancreatic Adenocarcinoma, metastatic, chemo-naive, phase II
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimasertibDrug
Also called MSC1936369B (MEK Inhibitor)
GemcitabineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-in Part: Regimen 1 | Experimental | Subjects will receive pimasertib capsule orally once daily (qd) doses of 15, 30, 45, 68, 90, and 120 milligram (mg) on Day 1, 2, 3, 4, 5, 8, 9, 10, 11, 12, 15,16, 17, 18, 19, 22, 23, 24, 25, 26 and gemcitabine 1000 milligram per square meter (mg/m^2) intravenous (IV) infusion for 30 minutes on Days 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (1 Cycle = 8 weeks). Receives: Drug: Pimasertib; Drug: Gemcitabine |
| Safety Run-in Part: Regimen 2 | Experimental | Subjects will receive pimasertib capsule orally twice daily (bid) doses of 60 and 75 mg continuously for a 28-day cycle and gemcitabine 1000 mg/m^2 intravenous (IV) infusion for 30 minutes on Days 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (1 Cycle = 8 weeks) (bid - continuous regimen). Receives: Drug: Pimasertib; Drug: Gemcitabine |
| Phase II: Arm 1 (Gemcitabine + Placebo) | Active comparator | Subjects will receive gemcitabine 1000 mg/m^2 IV infusion on for 30 minutes on Day 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (Cycle 1) then on Days 1, 8, and 15 of a 28-day cycle and placebo matched to pimasertib orally bid - continuous regimen. Receives: Drug: Gemcitabine; Drug: Placebo |
| Phase II: Arm 2 (Gemcitabine + Pimasertib) | Experimental | Subjects will receive gemcitabine 1000 mg/m^2 IV infusion for 30 minutes on Day 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (Cycle 1) then on Days 1, 8, and 15 of a 28-day cycle and pimasertib capsule orally bid - continuous regimen. Receives: Drug: Pimasertib; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Run-In Part: Number of Subjects With Dose Limiting Toxicities (DLTs)
DLT using the National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) v3.0,was defined as any of the following toxicities at any dose level and judged to be possibly or probably related to trial medication by the Investigator and/or the Sponsor and relevant for the combination treatment: Grade 3/more non-hematological toxicity excluding: Subjects with liver involvement: Grade 4 asymptomatic increases in liver function tests and subject without liver involvement: Grade 3 asymptomatic increases in liver function tests reversible within 7 days. Grade 3 vomiting encountered despite adequate therapy. Grade 3 diarrhea encountered despite adequate anti diarrhea therapy. Grade 4 neutropenia greater (>) 5 days duration or febrile neutropenia lasting for more than 1 day. Grade 4 thrombocytopenia > 1 day/Grade 3 with bleeding. Grade 4 anemia: Any treatment delay > 2 weeks due to drug-related adverse effects.
Measured: Up to 28 days in Cycle 1
Phase II: Progression-Free Survival (PFS) Time
PFS was defined as the time from randomization to the first documentation of objective tumor progression (Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline, Progressive Disease (PD): At least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started, or the appearance of 1 or more new lesions and stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started) or to death due to any cause, whichever occurred first. PFS calculated as (Months) = Date of first PD or death or censoring date minus date of randomization plus 1) divided by 30.4375.
Measured: From the time of randomization to every 8 weeks up to end of treatment (EOT) (6 years)
Secondary outcomes (27)
Safety Run-In Part: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation
An adverse event (AE) was any untoward medical occurrence in a subjects who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All AEs (serious and non-serious) except AEs recorded with an onset date prior to the first day of drug administration unless a worsening of the event was recorded after the first dosing date, in which case the event was counted as a TEAE. TEAEs include both SAEs and non-SAEs.
Measured: From the first dose of study drug administration until EOT (6 years)
Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) for Regimen 1
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
Plasma decay half-life was the time measured for the plasma concentration to decrease by one half.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Area Under Curve (AUC: 0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
AUC:0 to infinity was a measure of the serum concentration of the drug over time. It was used to characterize drug absorption.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine
Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 1
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 1
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 1
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 1
Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 1
ERK phosphoprotein in peripheral blood monocytes (PBMCs) was analyzed from blood samples of all subjects in the SAF analysis set (safety-run part) only.
Measured: pre-dose on Day 1, 2, 22 of Cycle 1; post-dose on Day 1, 22 of Cycle 1
Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Area Under Curve (AUC:0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) Regimen 2
AUC:0 to infinity is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine
Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 2
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 2
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 2
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 2
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 2
ERK phosphoprotein in peripheral blood monocytes (PBMCs) was analyzed from blood samples of all subjects in the SAF analysis set (safety-run part) only.
Measured: pre-dose on Day 1, 2, 22 of Cycle 1; post-dose on Day 1, 22 of Cycle 1
Phase II: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All AEs (serious and non-serious) except AEs recorded with an onset date prior to the first day of drug administration unless a worsening of the event was recorded after the first dosing date, in which case the event was counted as a TEAE. TEAEs include both SAEs and non-SAEs.
Measured: From the first dose of study drug administration until EOT (6 years)
Phase II: Percentage of Subjects With Best Overall Response (BOR)
Best overall response was defined as the presence of at least one complete response (CR), partial response (PR) or Stable Disease (SD) (using RECIST v1.0) during treatment. CR: Disappearance of all target lesions, PR: At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline and SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.
Measured: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)
Phase II: Percentage of Subjects With Clinical Benefit
Clinical Benefit was defined as the presence of at least one CR, PR or Stable Disease (SD) (using RECIST v1.0) during treatment. CR: Disappearance of all target lesions, PR: At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline and SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.
Measured: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)
Phase II: Time to Progression (TTP)
Time to progression (TTP) is defined as the time (in months) from the randomization date to the date of progression prior to the start of any subsequent therapy for the primary disease, as reported and documented by the Investigator (i.e. radiological progression per RECIST).
Measured: From randomization every 8 weeks up to EOT (6 years)
Phase II: Overall Survival (OS) Time
Overall survival (OS) time is defined as the time (in months) from randomization to death.
Measured: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Absorption Rate Constant (ka) of Pimasertib (MSC1936369B)
Measured: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Clearance From Central Compartment (CL/f) and Intercompartmental Clearance (Q/f) of Pimasertib (MSC1936369B)
Measured: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Volume of Central Compartment (V1/f) and Volume of Peripheral Compartment (V2/f) of Pimasertib (MSC1936369B)
Measured: Baseline, every 8 weeks up to EOT (6 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2009 (estimated)
- Study start30 Nov 2009
- Primary completion31 Dec 2013
- Study completion30 Apr 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic AdenocarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01016483
- Sponsor's protocol ID
- EMR200066_003
- Other IDs
- 2009-011992-61, 2009
- Status last verified
- Jul 2017
- First submitted
- 18 Nov 2009
- Last updated
- 13 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Van Cutsem E, Hidalgo M, Canon JL, Macarulla T, Bazin I, Poddubskaya E, Manojlovic N, Radenkovic D, Verslype C, Raymond E, Cubillo A, Schueler A, Zhao C, Hammel P. Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. Int J Cancer. 2018 Oct 15;143(8):2053-2064. doi: 10.1002/ijc.31603. Epub 2018 Aug 9.
PubMed 29756206
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Trial of MEK Inhibitor MSC1936369B or Placebo Combined With Gemcitabine in Metastatic Pancreas Cancer Subjects
- ClinicalTrials.gov ID
- NCT01016483
- Acronym / sponsor ID
- EMR200066_003
- Conditions
- Pancreatic Adenocarcinoma
- Keywords
- MEK inhibitor, cancer, pancreatic Adenocarcinoma, metastatic, chemo-naive, phase II
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 30 Nov 2009 (actual)
- Primary completion
- 31 Dec 2013 (actual)
- Study completion
- 30 Apr 2015 (actual)
- First posted
- 19 Nov 2009 (estimated)
- Results
- Posted 23 Jun 2017
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 treatment MSC1936369B in combination with Gemcitabine, in subjects with metastatic pancreatic adenocarcinoma. The study will be run in two parts:
Safety Run-In: Will determine the Maximum Tolerated Dose (MTD) and the recommended Phase II dose of MSC1936369B, when combined with gemcitabine, in subjects with metastatic pancreatic adenocarcinoma.
Phase II: Will assess the anti-tumor activity of MSC1936369B combined with gemcitabine compared to gemcitabine alone as first line treatment in subjects with metastatic pancreatic adenocarcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Safety Run-in Part: Regimen 1 | Experimental | Drug: Pimasertib, Drug: GemcitabineSubjects will receive pimasertib capsule orally once daily (qd) doses of 15, 30, 45, 68, 90, and 120 milligram (mg) on Day 1, 2, 3, 4, 5, 8, 9, 10, 11, 12, 15,16, 17, 18, 19, 22, 23, 24, 25, 26 and gemcitabine 1000 milligram per square meter (mg/m^2) intravenous (IV) infusion for 30 minutes on Days 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (1 Cycle = 8 weeks). |
| Safety Run-in Part: Regimen 2 | Experimental | Drug: Pimasertib, Drug: GemcitabineSubjects will receive pimasertib capsule orally twice daily (bid) doses of 60 and 75 mg continuously for a 28-day cycle and gemcitabine 1000 mg/m^2 intravenous (IV) infusion for 30 minutes on Days 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (1 Cycle = 8 weeks) (bid - continuous regimen). |
| Phase II: Arm 1 (Gemcitabine + Placebo) | Active comparator | Drug: Gemcitabine, Drug: PlaceboSubjects will receive gemcitabine 1000 mg/m^2 IV infusion on for 30 minutes on Day 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (Cycle 1) then on Days 1, 8, and 15 of a 28-day cycle and placebo matched to pimasertib orally bid - continuous regimen. |
| Phase II: Arm 2 (Gemcitabine + Pimasertib) | Experimental | Drug: Pimasertib, Drug: GemcitabineSubjects will receive gemcitabine 1000 mg/m^2 IV infusion for 30 minutes on Day 1, 8, 15, 22, 29, 36, and 43 followed by a 1-week rest (Cycle 1) then on Days 1, 8, and 15 of a 28-day cycle and pimasertib capsule orally bid - continuous regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject has provided signed informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments.
- Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas and availability of tumor sample.
- Evidence of disease (not necessarily measurable disease). Complete tumor assessment including chest X ray, CT scan of abdomen and other scans as necessary to document all sites of disease performed within 28 days prior to trial entry/randomization.
- Age ≥ 18 years.
- Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential is defined as: "All female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive."
Key exclusion criteria (8 listed)
- Bone marrow impairment as evidenced by hemoglobin less (<) 9.0 gram per deciliter (g/dL), neutrophil count < 1.5 x 10^9/ liter (L), platelets < 100 x 10^9/L.
- Renal impairment as evidenced by serum creatinine > 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance < 60 mL/min.
- Liver function abnormality as defined by total bilirubin > 1.5 x ULN, or aspartate aminotransferase/ alanine aminotransferase (AST/ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN.
- Serum calcium > 1 x ULN.
- History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases, is stable by CT scan without evidence of cerebral edema, and has no requirements for corticosteroids or anticonvulsants.
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: MSC1936369B (MEK Inhibitor) | Drug | Phase II: Arm 2 (Gemcitabine + Pimasertib), Safety Run-in Part: Regimen 1, Safety Run-in Part: Regimen 2 |
| Gemcitabine | Drug | Phase II: Arm 1 (Gemcitabine + Placebo), Phase II: Arm 2 (Gemcitabine + Pimasertib), Safety Run-in Part: Regimen 1, Safety Run-in Part: Regimen 2 |
| Placebo | Drug | Phase II: Arm 1 (Gemcitabine + Placebo) |
Primary outcome
Safety Run-In Part: Number of Subjects With Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days in Cycle 1
DLT using the National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) v3.0,was defined as any of the following toxicities at any dose level and judged to be possibly or probably related to trial medication by the Investigator and/or the Sponsor and relevant for the combination treatment: Grade 3/more non-hematological toxicity excluding: Subjects with liver involvement: Grade 4 asymptomatic increases in liver function tests and subject without liver involvement: Grade 3 asymptomatic increases in liver function tests reversible within 7 days. Grade 3 vomiting encountered despite adequate therapy. Grade 3 diarrhea encountered despite adequate anti diarrhea therapy. Grade 4 neutropenia greater (>) 5 days duration or febrile neutropenia lasting for more than 1 day. Grade 4 thrombocytopenia > 1 day/Grade 3 with bleeding. Grade 4 anemia: Any treatment delay > 2 weeks due to drug-related adverse effects.
Phase II: Progression-Free Survival (PFS) Time
Time frame: From the time of randomization to every 8 weeks up to end of treatment (EOT) (6 years)
PFS was defined as the time from randomization to the first documentation of objective tumor progression (Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline, Progressive Disease (PD): At least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started, or the appearance of 1 or more new lesions and stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started) or to death due to any cause, whichever occurred first. PFS calculated as (Months) = Date of first PD or death or censoring date minus date of randomization plus 1) divided by 30.4375.
27 secondary outcomes
Safety Run-In Part: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation
Time frame: From the first dose of study drug administration until EOT (6 years)
Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) for Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Area Under Curve (AUC: 0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine
Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 1
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 1
Time frame: pre-dose on Day 1, 2, 22 of Cycle 1; post-dose on Day 1, 22 of Cycle 1
Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Area Under Curve (AUC:0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine
Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 2
Time frame: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1
Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 2
Time frame: pre-dose on Day 1, 2, 22 of Cycle 1; post-dose on Day 1, 22 of Cycle 1
Phase II: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation
Time frame: From the first dose of study drug administration until EOT (6 years)
Phase II: Percentage of Subjects With Best Overall Response (BOR)
Time frame: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)
Phase II: Percentage of Subjects With Clinical Benefit
Time frame: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)
Phase II: Time to Progression (TTP)
Time frame: From randomization every 8 weeks up to EOT (6 years)
Phase II: Overall Survival (OS) Time
Time frame: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Absorption Rate Constant (ka) of Pimasertib (MSC1936369B)
Time frame: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Clearance From Central Compartment (CL/f) and Intercompartmental Clearance (Q/f) of Pimasertib (MSC1936369B)
Time frame: Baseline, every 8 weeks up to EOT (6 years)
Phase II: Volume of Central Compartment (V1/f) and Volume of Peripheral Compartment (V2/f) of Pimasertib (MSC1936369B)
Time frame: Baseline, every 8 weeks up to EOT (6 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29756206Van Cutsem E, Hidalgo M, Canon JL, Macarulla T, Bazin I, Poddubskaya E, Manojlovic N, Radenkovic D, Verslype C, Raymond E, Cubillo A, Schueler A, Zhao C, Hammel P. Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. Int J Cancer. 2018 Oct 15;143(8):2053-2064. doi: 10.1002/ijc.31603. Epub 2018 Aug 9.
Related trials for Pancreatic Adenocarcinoma
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
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
Merck KGaA, Darmstadt, Germany
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pimasertib and Gemcitabine in people with Pancreatic Adenocarcinoma, run by EMD Serono at 2 sites in 2 countries.
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 6 inclusion and 8 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: finished, as of the sponsor's last update on 13 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Germany. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 23 Jun 2017). 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?
Safety Run-In Part: Number of Subjects With Dose Limiting Toxicities (DLTs) (time frame: Up to 28 days in Cycle 1). The study lists 2 primary outcomes in all. 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 NCT01016483, which also lists 1 linked publication.
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 13 Jul 2017.