Overview

This trial is active, not recruiting.

Conditions pik3ca mutated advanced solid tumors,, pik3ca amplified advanced solid tumors
Treatments byl719, amg 479
Phase phase 1/phase 2
Targets IGF1-R, PI3K
Sponsor Novartis Pharmaceuticals
Collaborator NantCell, Inc.
Start date November 2012
End date June 2017
Trial size 47 participants
Trial identifier NCT01708161, 2012-001962-13, CBYL719X2105J

Summary

This is a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part is to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up. At a minimum, patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
For: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients will be enrolled sequentially until an MTD or a recommended Phase II dose could be defined. All patients will receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients will receive the same combination treatment.
byl719
BYL719 is a small molecule inhibiting PI3-Kinase.
amg 479 ganitumab
AMG 479 is a monoclonal antibody directed against IGF1-R.

Primary Outcomes

Measure
Incidence of dose limiting toxicities (DLTs)
time frame: Cycle 1 (initial 28 days of treatment)
Objective response rate (ORR)
time frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment

Secondary Outcomes

Measure
Disease control rate (DCR)
time frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment
Duration of response (DOR)
time frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment
Progression free survival (PFS)
time frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment
Number of patients with Adverse Events (AEs)
time frame: baseline, up to 30 weeks
Number of patients with Serious Adverse Events (SAEs)
time frame: Baseline, up to 30 weeks
Change in hematology and chemistry values
time frame: baseline, up to 30 weeks
Change in vital signs
time frame: baseline, up to 30 weeks
Change in electrocardiograms (ECGs)
time frame: baseline, up to 30 weeks
Plasma/serum concentration versus time profiles
time frame: Cycle 1 Day 1, Cycle 1 Day 15
Derived basic pharmacokinetics paramaeters of BYL719 and AMG479
time frame: Cycle 1 Day 1, Cycle 1 Day 15
Overall survival
time frame: Baseline, up to end of treatment plus 30 days

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: - Written informed consent. - Patients aged ≥ 18 years (male or female). - Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue: - Hormone receptor positive breast carcinoma - Ovarian carcinoma - Other tumors upon agreement with sponsor - Adequate organ function - Negative serum pregnancy test Exclusion criteria: - Patients with known history of severe infusion reactions to monoclonal antibodies. - Patients with primary CNS tumor or CNS tumor involvement. - History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment. - Clinically significant cardiac disease. - History of another malignancy within last 2 years. - Pregnant or nursing (lactating) women. Other protocol-defined inclusion/exclusion criteria may apply.

Additional Information

Official title A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
Description This is a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part is to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). Once MTD/RP2D has been determined, patients will be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma will be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma will be enrolled in Arm 2. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up. At a minimum, patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Novartis.