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A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
This study is ongoing, but not recruiting participants.
Sponsor:
Novartis Pharmaceuticals
Collaborator:
NantCell, Inc.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01708161
First received: September 19, 2012
Last updated: March 23, 2017
Last verified: March 2017
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| PIK3CA Mutated Advanced Solid Tumors PIK3CA Amplified Advanced Solid Tumors | Drug: BYL719 Drug: AMG 479 | Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment |
| Official Title: | A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors |
Resource links provided by NLM:
Further study details as provided by Novartis ( Novartis Pharmaceuticals ):
Primary Outcome Measures:
- Incidence of dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (initial 28 days of treatment) ]Phase lb only
- Objective response rate (ORR) [ Time Frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment ]Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter
Secondary Outcome Measures:
- Disease control rate (DCR) [ Time Frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment ]As per RECIST 1.1 (phase lb & ll)
- Duration of response (DOR) [ Time Frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment ]As per RECIST 1.1 (Phase lb & ll)
- Progression free survival (PFS) [ Time Frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment ]As per RECIST 1.1 (phase lb & ll)
- Number of patients with Adverse Events (AEs) [ Time Frame: baseline, up to 30 weeks ]phase lb & ll
- Number of patients with Serious Adverse Events (SAEs) [ Time Frame: Baseline, up to 30 weeks ]phase lb & ll
- Change in hematology and chemistry values [ Time Frame: baseline, up to 30 weeks ]phase lb & ll
- Change in vital signs [ Time Frame: baseline, up to 30 weeks ]phase lb & ll
- Change in electrocardiograms (ECGs) [ Time Frame: baseline, up to 30 weeks ]phase lb & ll
- Plasma/serum concentration versus time profiles [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 ]Plasma concentration for BYL719; Serum concentration for AMG 479 (ganitumab); cycle 1 = initial 28 days of treatment
- Derived basic pharmacokinetics paramaeters of BYL719 and AMG479 [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 ]Standard non-compartmental PK parameters e.g. AUC, Cmax, apparent terminal elimination half-life; cycle 1 = initial 28 days of treatment
- Overall survival [ Time Frame: Baseline, up to end of treatment plus 30 days ]Phase II only, no survival follow-up after end of treatment plus 30 days
| Enrollment: | 47 |
| Actual Study Start Date: | November 27, 2012 |
| Estimated Study Completion Date: | June 30, 2017 |
| Estimated Primary Completion Date: | June 30, 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BYL719 + AMG 479
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.
|
Drug: BYL719
BYL719 is a small molecule inhibiting PI3-Kinase.
Drug: AMG 479
AMG 479 is a monoclonal antibody directed against IGF1-R.
Other Name: ganitumab
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01708161
Please refer to this study by its ClinicalTrials.gov identifier: NCT01708161
Locations
| United States, California | |
| University of California at Los Angeles TORI | |
| Los Angeles, California, United States, 90095 | |
| United States, Massachusetts | |
| Massachusetts General Hospital Mass General 2 | |
| Boston, Massachusetts, United States, 02114 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center MSKCC 5 | |
| NY, New York, United States, 10065 | |
| United States, Tennessee | |
| Sarah Cannon Research Institute SCRI 3 | |
| Nashville, Tennessee, United States, 37203 | |
| Belgium | |
| Novartis Investigative Site | |
| Leuven, Belgium, 3000 | |
| Canada, Ontario | |
| Novartis Investigative Site | |
| Toronto, Ontario, Canada, M5G 1Z6 | |
| Spain | |
| Novartis Investigative Site | |
| Sevilla, Andalucia, Spain, 41013 | |
| Novartis Investigative Site | |
| Barcelona, Catalunya, Spain, 08035 | |
| Novartis Investigative Site | |
| Madrid, Spain, 28033 | |
| Novartis Investigative Site | |
| Madrid, Spain, 28041 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
NantCell, Inc.
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01708161 History of Changes |
| Other Study ID Numbers: |
CBYL719X2105J 2012-001962-13 ( EudraCT Number ) |
| Study First Received: | September 19, 2012 |
| Last Updated: | March 23, 2017 |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
|
PIK3CA mutation advanced solid tumor breast cancer ovarian cancer |
Additional relevant MeSH terms:
|
Neoplasms Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 26, 2017