Phase Ib trial of the combination of PI3K inhibitor BAY 80-6946 and allosteric-MEK inhibitor BAY 86-9766 in subjects with advanced cancer

Completed

• Conditions: gevorderde kanker; Malignant solid tumor / advanced cancer; 10027656

• Registration Number: NL-OMON39510
• Lead Sponsor: Bayer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 25

Inclusion Criteria

- The informed consent must be signed before any study specific tests or procedures are initiated
- Subjects, at least 18 years of age, with incurable and refractory advanced or metastatic solid tumors that have progressed on or failed to respond to therapies known to provide clinical benefit
- Histological or cytological documentation of non-hematologic, malignant solid tumor, excluding primary brain or spinal tumors, with no current involvement in the central nervous system. Subjects who have brain metastases that have been treated and have been stable for > 3 months may be included in the study
- At least one measurable lesion or evaluable disease, as per RECIST 1.1
- ECOG Performance Status of 0 or 1
- Life expectancy of at least 12 weeks
- LVEF >= LLN (Lower Limit of Normal) for the Institution
- Women of childbearing age and men enrolled in this study must use adequate birth control measures prior to, during the course of the study and 30 days after the last administration of either BAY 80-6946 or BAY 86-9766. An adequate contraception includes a hormonal contraception with implants or combined oral, transdermal, or injectable contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of the partner. In addition the use of condoms for subjects or their partners is required unless the woman has had a hysterectomy
- ALT and AST <= 2.5 x ULN (<= 5 x ULN for subjects with liver involvement of their cancer)
- Total bilirubin <= 1.5 x ULN
- Serum creatinine <= 1.5 x ULN
- PT-INR/PTT < 1.5 x upper limit of normal (Subjects who are being therapeutically
anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists).Low-dose aspirin is permitted (<= 100 mg daily)
- Adequate bone marrow function as assessed by the following:
- Hemoglobin >= 9.0 g/dL (transfusion permitted)
- Absolute neutrophil count (ANC) >= 1,500/mm3
- Platelet count >= 100,000/mm3
- Ability to understand and follow study-related instructions
- Only for subjects enrolled into the expansion cohort(s): Presence of a tumor mutation in one or more of the following genes: KRAS, NRAS, BRAF, or PI3KCA

Exclusion Criteria

• Ability to understand andfollow study related instructions;Subjects are to be excluded from the study if they display any of the following criteria:;•History of Retinal Vein Occlusion or eye exam showing risk factor;•History of cardiac disease congestive heart failure(CHF)>NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy. ;•Current diagnosis of Type 1 or 2 Diabetes Mellitus, or fasting blood glucose > 125 mg/dL, or HgBA1c > = 7.0;•Use of systemic corticosteroid medication within 2 weeks of the start of study treatment (topical or inhaled steroids are permitted). Single doses of systemic corticosteroids given as pre-medication for procedures or nonstudy drugs may be administered up to 24 hours of first dosing of BAY 80-6946 ;•Active clinically serious infections, including viral hepatitis, > Grade 2 (NCI CTCAE Version 4.0) ;•Uncontrolled seizure disorder;•Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.;•Known human immunodeficiency virus (HIV) infection;•Subjects undergoing renal dialysis;•Known bleeding diathesis;•Ongoing substance abuse, medical, psychological or social conditions that may interfere with the subject*s participation in the study or evaluation of the study results;•Pregnant or breast feeding women. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days before the start of treatment.;•Women of childbearing age and men enrolled in this study must use adequate birth control measures prior to, during the course of the study and 30 days after the last administration of either BAY 80-9766 or BAY 86-9766. An adequate contraception includes a hormonal contraception with implants or combined oral, transdermal or injectable contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of the partner. In addition the use of condoms for subjects or their partners is required unless the woman has had a hysterectomy.;•Use of strong inhibitors of CYP3A4, (eg, ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (eg, St. John*s Wort, rifampin) are prohibited within 2 weeks of starting study treatment and for the duration of the study.;• Known G6PD deficiency

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary variables being evaluated include, safety, tolerability,<br /><br>pharmacokinetics and recommended Phase II dose for the combination of BAY<br /><br>80-6946 and BAY 86-9766. (protocol page 47)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Not applicable</p><br>