Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Condition: Neoplasm
MeSH terms: Neoplasms
Intervention: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg; Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg; Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg; Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg; Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg; HCC Child-Pugh A expansion cohort: Regorafenib 100 mg; HCC Child-Pugh B expansion cohort: Regorafenib 100 mg; NSCLC expansion cohort: Regorafenib 100 mg
Intervention description: Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral co-precipitate (CP) tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.; Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
Phase: Phase 1
Study type: Interventional
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Oncology patients with advanced disease; BAY73-4506

Summary:

      Continuous dosing of BAY73-4506 in patients with advanced cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years

          -  Patients with advanced, histologically or cytologically confirmed solid tumors,
             malignant lymphomas, or multiple myeloma refractory to any standard therapy

          -  Radiographical, hematological or clinically evaluable tumor

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

          -  Life expectancy of at least 12 weeks

          -  Adequate bone marrow, liver, and renal function as assessed by the following
             laboratory requirements:

               -  Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

          -  Signed informed consent must be obtained prior to any study specific procedures

        Exclusion Criteria:

          -  History of cardiac disease: congestive heart failure (CHF) > New York Heart
             Association (NYHA) Class II; active coronary artery disease, myocardial infarction
             within 6 months prior to study entry; new onset angina within 3 months or unstable
             angina or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or
             digoxin are permitted)

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or
             diastolic blood pressure > 90 mmHg, despite optimal medical management

          -  History of HIV infection or chronic hepatitis B or C

          -  Active clinically serious infections (> Grade 2 NCI Common Terminology Criteria for
             Adverse Events v3.0)

          -  Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from
             definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks
             prior to study entry and is clinically stable with respect to the tumor at the time of
             study entry. Patients with brain metastases must not be undergoing acute steroid
             therapy or steroid taper (chronic steroid therapy is acceptable provided that the dose
             is stable for one month prior to and following screening radiographic studies)

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the patient178s participation in the study or evaluation of the study results

          -  Radiotherapy to the target lesions within 3 weeks prior to Day 1, Cycle 1 (first dose
             of study drug). (Palliative radiotherapy will be allowed). Radiotherapy to the target
             lesions during study will be regarded as progressive disease

          -  Previous or concurrent cancer which is distinct in primary site or histology from the
             cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
             cell carcinoma, superficial bladder tumors [Ta, Tis and T1] or any cancer curatively
             treated > 3 years prior to study entry.