Pancreatic Neoplasms
Conditions
Keywords
pancreatic cancer,, MEK-inhibitor
Brief summary
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.
Interventions
DRUGBAY86-9766+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)
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Tumor Response: Investigator Assessment: Phase I | 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 |
| Time to Progression (TTP): Phase II | 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 |
Countries
Belgium, Czechia, France, Germany, Italy, Norway, Poland, United Kingdom, United States
Outcome results
None listed