Refametinib (BAY86-9766) in Combination With Regorafenib (Stivarga, BAY73-4506) in Patients With Advanced or Metastatic Cancer
Neoplasms
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Patients with Cancer
Eligibility Criteria
Inclusion Criteria:
Criteria for the Phase 1b:
- Patients with locally advanced or metastatic solid tumors who have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; is not a candidate for, or is unwilling to undergo, standard therapy in cases where no curative option exists.
Cohort-specific criteria for Phase 2:
- CRC (Colorectal cancer): Patients with metastatic CRC and known KRAS (Kirsten rat sarcoma viral oncogene homolog) status who are eligible for treatment with regorafenib in accordance with the approved labeling.
- NSCLC (Non-small-cell lung cancer): Patients with NSCLC and known KRAS status after platinum based chemotherapy.
- Breast cancer: Patients with Her-2 negative breast cancer after anthracycline and taxane based chemotherapy.
- Baseline tumor tissue to conduct molecular and / or genetic studies should be available from all study patients enrolled in this study. (optional in Phase 1b)
- Patients must have at least one uni-dimensional measurable lesion by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1. (applicable only in Phase 2)
- Male or female patients ≥ 18 years of age (only female patients in breast cancer cohort of Phase 2).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy of at least 3 months
- Adequate bone marrow, liver and renal function
- Cardiac function within normal range
Exclusion Criteria:
- Prior treatment with refametinib or regorafenib.
- Metastatic brain or meningeal tumors
- Uncontrolled hypertension despite optimal medical management
- History of cardiac disease
- Arterial or venous thrombotic or embolic events
- Any hemorrhage or bleeding event
- History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
- Any condition that was unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
Excluded previous therapies and medications:
- Radiotherapy within 3 weeks prior to start of treatment
- Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is shorter (or within 6 weeks for mitomycin C) before start of the study treatment
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Ph1b-Refametinib/Regorafenib Cohort 0
Ph1b-Refametinib/Regorafenib Cohort -1
Ph1b-Refametinib/Regorafenib Cohort -1a
Phase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort 0: Refametinib 30mg twice daily (b.i.d) + Regorafenib 80mg once daily (q.d), 3 weeks on/1 week off.
Phase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort -1: Refametinib 20mg b.i.d + Regorafenib 80mg q.d, 3 weeks on/1 week off.
Phase 1b part of study: Participants received different doses of Refametinib and Regorafenib combination therapy to determine recommended Phase 2 dose (RP2D) via dose-escalation. Cohort -1a: Refametinib 20mg b.i.d + Regorafenib 120mg q.d, 3 weeks on/1 week off.