Trial of Gemcitabine With or Without MSC1936369B in Pancreatic Cancer

EMD Serono141 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

141

Conditions

Pancreatic Adenocarcinoma

Interventions

PimasertibDRUG

GemcitabineDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subject has provided signed informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments. 2. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas and availability of tumor sample. 3. 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. 4. Age ≥ 18 years. 5. 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." 6. 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. Exclusion Criteria: 1. 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. 2. Renal impairment as evidenced by serum creatinine \> 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance \< 60 mL/min. 3. 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. 4. Serum calcium \> 1 x ULN. 5. 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. 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than 1. 7. Significant cardiac conduction abnormalities, including QT interval corrected for heart rate (QTc) prolongation of \> 480 milliseconds (ms) and/or pacemaker. 8. Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis or history of retinal vein occlusion.

Locations (2)

For Recruiting Locations in the United States, please Contact U.S. Medical Information

Rockland, Massachusetts, United States

For Recruiting Locations outside the United States, Please contact the Merck KGaA Communication Center

Darmstadt, Germany

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From the time of randomization to every 8 weeks up to end of treatment (EOT) (6 years)

Secondary Outcomes

Safety Run-In Part: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation

Data from ClinicalTrials.gov

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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.

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