Trial of Gemcitabine With or Without MSC1936369B in Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Merck KGaA
Sponsor:
Collaborator:
Merck Serono S.A., Geneva
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01016483
First received: November 18, 2009
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Adenocarcinoma
Drug: MEK Inhibitor MSC1936369B
Drug: Gemcitabine and Placebo
Drug: Gemcitabine and MEK Inhibitor MSC1936369B
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Safety Run-In Part: To determine the Maximum Tolerated Dose and the Recommended Phase II Dose of MSC1936369B when combined with gemcitabine in subjects with metastatic pancreatic adenocarcinoma for each of the two treatment regimens. [ Time Frame: 1 Years ] [ Designated as safety issue: No ]
  • Phase II Part: To evaluate the anti-tumor activity of MSC1936369B combined with gemcitabine, compared to gemcitabine alone as first line treatment in subjects with metastatic pancreatic adenocarcinoma. [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To provide preliminary findings on the safety profile of MSC1936369B combined with gemcitabine in subjects with metastatic pancreatic adenocarcinoma for each of the two treatment regimens. [ Time Frame: 1 Years ] [ Designated as safety issue: No ]
  • Safety Run-In Part: To assess the pharmacokinetics (PK) of MSC1936369B and gemcitabine, when combined in subjects with metastatic pancreatic cancer. [ Time Frame: 1 Years ] [ Designated as safety issue: No ]
  • Safety Run-In Part: To assess changes in pharmacodynamic (Pd) markers (e.g. phospho-ERK in peripheral blood mononuclear cells [PBMCs]). [ Time Frame: 1 Years ] [ Designated as safety issue: No ]
  • Phase II Part: To determine the safety and tolerability of MSC1936369B combined to gemcitabine in subjects with metastatic pancreatic cancer. [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]
  • Phase II Part: To evaluate the anti-tumor activity in each treatment arm in terms of response rate, clinical benefit, overall survival and time to progression. [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]
  • Phase II Part: To assess the pharmacokinetics (PK) of MSC1936369B and gemcitabine, when given in combination in subjects with metastatic pancreatic adenocarcinoma [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]
  • Phase II Part: To assess changes in pharmacodynamics (Pd) markers (e.g. phosphor-ERK in peripheral blood mononuclear cells [PBMCs]) [ Time Frame: 2.5 Years ] [ Designated as safety issue: No ]

Estimated Enrollment: 174
Study Start Date: November 2009
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Safety Run-In, Single Arm: Drug: MEK Inhibitor MSC1936369B

Two different dosing regimens of MSC1936369B will be tested.

QD-5 On/ 2 Off Regimen: MSC1936369B dose escalation treatment will be given orally once daily on day 1 to 5 and then no medication on day 6 and 7, that means 5 days on, 2 days off. Patients will continue on day 8 to 12, 15 to 19 and 22 to 26, and so on up to day 56 (first cycle) or day 28 (all other cycles).

BID - Continuous Regimen: MSC1936369B dose escalation treatment will be given orally twice-per-day as continuous daily dosing from day 1 to day 28. There will be no treatment breaks, unless required due to toxicity or adverse events.

Other Name: Pimasertib
Experimental: Phase II, Arm 1: Drug: Gemcitabine and Placebo

Gemcitabine: 1000 mg/m² 30 minutes i.v. infusion on days 1, 8, 15, 22, 29, 36 and 43 followed by 1 week rest (56-day cycle 1) then on Days 1, 8 and 15 of the following 28-day cycles.

AND Placebo orally.

Only one of the doses and regimens will be selected for continuation in the Phase II part of the trial based on the outcome of the Safety Run-In part.

Experimental: Phase II, Arm 2: Drug: Gemcitabine and MEK Inhibitor MSC1936369B

Gemcitabine: 1000 mg/m² 30 minutes i.v. infusion on days 1, 8, 15, 22, 29, 36 and 43 followed by 1 week rest (56-day cycle 1)then on Days 1, 8 and 15 of the following 28-day cycle.

AND MSC1936369B orally.

Only one of the doses and regimens will be selected for continuation in the Phase II part of the trial based on the outcome of the Safety Run-In part.

Other Name: Pimasertib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 < 9.0 g/dL, neutrophil count < 1.5 x 10^9/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 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 QTc prolongation of > 480 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01016483

Contacts
Contact: Bernard Laffranchi, MD Bernard.Laffranchi@mereckgroup.com
Contact: Thea Faivre, PhD Thea.Faivre@merckgroup.com

Locations
Germany
Please contact Merck KGaA Communication Center located in Recruiting
Darmstadt, Germany, for EU Recruiting Sites, Germany
Contact       service@merck.de   
Sponsors and Collaborators
Merck KGaA
Merck Serono S.A., Geneva
Investigators
Study Director: Bernard Laffranci MD Merck Serono S.A., Geneva
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01016483     History of Changes
Other Study ID Numbers: EMR200066_003
Study First Received: November 18, 2009
Last Updated: January 17, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Ministry of Social Affairs, Public Health and the Environment
Belgium: Institutional Review Board
Spain: Comité Ético de Investigación Clínica
Spain: Ministry of Health

Keywords provided by Merck KGaA:
MEK inhibitor
cancer
pancreatic Adenocarcinoma
metastatic
chemo-naive
phase II

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 23, 2014