Combination With Gemcitabine in Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Multi-center, Phase I/II Study of BAY86-9766 in Combination With Gemcitabine in Patients With Locally Advanced Inoperable or Metastatic Pancreatic Cancer

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: BAY86-9766+Gemcitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: BAY86-9766+Gemcitabine<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Dose Limiting Toxicities (DLT): Phase I |  | From randomization up to the first 8 weeks of therapy | 
| Tumor Response (Adjudicated Blinded Read Assessment): Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response: Investigator Assessment: Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Disease Control (DC): Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Disease Control (DC): Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Duration of Response (DOR): Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Duration of Response: Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Time to Progression (TTP): Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Time to Progression (TTP): Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Progression-Free Survival (PFS): Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Progression-Free Survival (PFS): Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Overall Survival (OS): Phase I |  | From start of treatment until 134 weeks assessed every 8 weeks | 
| Overall Survival (OS): Phase II |  | From start of treatment until 134 weeks assessed every 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer,, MEK-inhibitor