Combination With Gemcitabine in Advanced Pancreatic Cancer (BAGPAC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01251640
First received: November 8, 2010
Last updated: July 1, 2015
Last verified: July 2015
  Purpose

Open-label, uncontrolled, Phase I/II study to evaluate safety and efficacy of BAY86-9766 plus gemcitabine in locally advanced, unresectable or metastatic pancreatic cancer.

Phase I: Dose escalation study investigating 20, 30 and 50 mg BAY86-9766 plus gemcitabine (1000mg/m2); determination of maximum tolerated dose and recommended phase 2 dose.

Phase II: Determination of response (RECIST 1.1; primary endpoint). Secondary endpoints: response duration, disease control rate, time to progression, progression-free survival, overall survival, safety and tolerability.

Tumor assessments at Screening and than every 8 weeks.; Safety evaluations at Screening and weekly throughout the study; Safety follow-up visit 30 days after the last dose of study treatment; Survival follow up monthly for up to 8 month after LPFV.


Condition Intervention Phase
Pancreatic Neoplasms
Drug: BAY86-9766+Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Phase I/II Study of BAY86-9766 in Combination With Gemcitabine in Patients With Locally Advanced Inoperable or Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of Subjects With Dose Limiting Toxicities (DLT): Phase I [ Time Frame: From randomization up to the first 8 weeks of therapy ] [ Designated as safety issue: Yes ]
  • Tumor Response (Adjudicated Blinded Read Assessment): Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor Response: Investigator Assessment: Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Disease Control (DC): Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Disease Control (DC): Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Duration of Response (DOR): Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Duration of Response: Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Time to Progression (TTP): Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Time to Progression (TTP): Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS): Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS): Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Overall Survival (OS): Phase I [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]
  • Overall Survival (OS): Phase II [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose: Phase I [ Time Frame: From start of the treatment upto the first eight weeks of therapy ]
  • Maximum Observed Drug Concentration in Plasma (Cmax) of Refametinib and Metabolite [ Time Frame: Cycle 1 Day 21, Cycle 1 Day 22 ]
  • Maximum Observed Drug Concentration in Plasma (Cmax) of Gemcitabine and its Metabolite [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 22 ]
  • Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Refametinib and Metabolite [ Time Frame: Cycle 1 Day 21, Cycle 1 Day 22 ]
  • Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Gemcitabine and its Metabolite [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 22 ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration AUC (0-tlast) of Refametinib and Metabolite [ Time Frame: Cycle 1 Day 21, Cycle 1 Day 22 ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration AUC (0-tlast) of Gemcitabine and its Metabolite [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 22 ]
  • Area Under the Curve From Time Zero to 8 hours [AUC (0-8)] of Refametinib and Metabolite [ Time Frame: Cycle 1 Day 21, Cycle 1 Day 22 ]
  • Area under the Concentration-Time Curve (AUC) of Gemcitabine and its Metabolite [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 22 ]
  • Half Life Associated With Terminal Slope (t1/2) of Refametinib and Metabolite [ Time Frame: Cycle 1 Day 21, Cycle 1 Day 22 ]
  • Half Life Associated With Terminal Slope (t1/2) of Gemcitabine and its Metabolite [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 22 ]
  • Number of Subjects With Improvement or Deterioration in Worst Pain: Phase I [ Time Frame: Cycle (C) 1 Day (D) 29 (C1D29), C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, End of treatment visit ]
  • Number of Subjects With Improvement or Deterioration in Worst Pain: Phase II [ Time Frame: Cycle (C) 2 Day (D) 1 (C2D1), C4D1, C6D1, C8D1, C10D1, C12D1, End of treatment visit ]
  • Number of Subjects With Pain Response: Phase I [ Time Frame: Cycle (C) 1 Day (D) 29 (C1D29), C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, End of treatment visit ]
  • Number of Subjects With Pain Response: Phase II [ Time Frame: Cycle (C) 2 Day (D) 1 (C2D1), C4D1, C6D1, C8D1, C10D1, C12D1, End of treatment visit ]
  • Brief Pain Inventory - Short Form (BPI-SF) score: Phase I [ Time Frame: Baseline, Cycle (C) 1 Day (D) 29 (C1D29), C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, End of treatment (EOT) visit ]
  • Brief Pain Inventory - Short Form (BPI-SF) score: Phase II [ Time Frame: Baseline,Cycle (C) 1 Day (D) 1 (C1D1), C1D29, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D9, C10D1, C11D1, C12D1, C13D1, End of treatment visit ]
  • Number of Subjects Recorded Pain Medication in Diary: Phase I [ Time Frame: Baseline, Cycle (C) 1 Day (D) 29 (C1D29), C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, End of treatment visit ]
  • Number of Subjects Recorded Pain Medication in Diary: Phase II [ Time Frame: Baseline, Cycle (C) 1 Day (D) 29 (C1D29), C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, End of treatment visit ]
  • Number of subjects with KRAS Mutational Status [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ]
  • Number of subjects with the BRAF loci Mutational Status [ Time Frame: From start of treatment until 134 weeks assessed every 8 weeks ]

Enrollment: 90
Study Start Date: January 2011
Study Completion Date: August 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: BAY86-9766+Gemcitabine
Phase I: 40 mg/day (20 mg twice daily), 60 mg/day (30 mg twice daily, 100 mg/day (50 mg bid) dependent on safety/tolerability Phase II: Recommended Phase II dose (RP2D) dependent on the results of the Phase I part of this study Route of administration: Oral, twice daily (bid) in combination with gemcitabine 1000 mg/m2 Intravenous infusion over 30 minutes weekly for seven out of eight weeks (Cycle 1); followed by 1000 mg/m2 Intravenous infusion over 30 minutes weekly for three out of four weeks (Cycle 2 and subsequent)

  Eligibility

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

Inclusion Criteria:

  • Male or female patients ≥18 years of age
  • Histological or cytologically confirmed locally advanced, inoperable or metastatic pancreatic adenocarcinoma not amenable to curative radiotherapy or surgery
  • Patients must have at least one uni-dimensional measurable lesion by CT or MRI according to RECIST, Version 1.1
  • Resolution of all acute toxic effects of any prior local treatment to Common Terminology Criteria for Adverse Events (CTCAE) Grade </= 1
  • Eastern Cooperative Oncology Group performance status (ECOG PS) </= 2
  • Patient has cardiac function, within normal range, as measured by an echocardiogram

Exclusion Criteria:

  • Known history of, or symptomatic metastatic brain or meningeal tumors
  • History of cardiac disease
  • Active clinically serious infections
  • Clinically significant (ie. symptomatic) peripheral vascular disease
  • Pregnant or lactating women; women of childbearing potential not employing adequate contraception
  • Use of strong inhibitors or inducers of CYP3A4
  • Prior systemic therapy for metastatic or locally advanced, unresectable pancreatic cancer, or other malignancy
  • Previous gemcitabine or 5-fluorouracil (5-FU) given concurrently as radiosensitizers to radiation therapy in adjuvant intention if given within 6 months from start of study treatment
  • Thrombotic or embolic events such within 6 months prior to start of study treatment
  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: NCT01251640

  Show 31 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01251640     History of Changes
Other Study ID Numbers: 14905, 2010-019588-12
Study First Received: November 8, 2010
Last Updated: July 1, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bayer:
pancreatic cancer,
MEK-inhibitor

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015