A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
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| ClinicalTrials.gov Identifier: NCT01708161 |
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Recruitment Status :
Completed
First Posted : October 16, 2012
Last Update Posted : May 14, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| PIK3CA Mutated Advanced Solid Tumors PIK3CA Amplified Advanced Solid Tumors | Drug: BYL719 Drug: AMG 479 | Phase 1 Phase 2 |
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was 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 were to be guided by a Bayesian Logistic Regression Model (BLRM).
Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 47 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| 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 |
| Actual Study Start Date : | November 27, 2012 |
| Actual Primary Completion Date : | December 26, 2014 |
| Actual Study Completion Date : | June 1, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: BYL719 + AMG 479
For: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients were to be enrolled sequentially until an MTD or a recommended Phase II dose were defined. All patients were to receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients were to receive the same combination treatment.
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Drug: BYL719
BYL719 is a small molecule inhibiting PI3-Kinase.
Other Name: ALPELISIB Drug: AMG 479 AMG 479 is a monoclonal antibody directed against IGF1-R.
Other Name: ganitumab |
- 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
- 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key 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
Key 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01708161
| United States, California | |
| Novartis Investigative Site | |
| Los Angeles, California, United States, 90095 | |
| United States, Massachusetts | |
| Novartis Investigative Site | |
| Boston, Massachusetts, United States, 02114 | |
| United States, New York | |
| Novartis Investigative Site | |
| New York, New York, United States, 10017 | |
| United States, Tennessee | |
| Novartis Investigative Site | |
| 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 | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01708161 History of Changes |
| Other Study ID Numbers: |
CBYL719X2105J 2012-001962-13 ( EudraCT Number ) |
| First Posted: | October 16, 2012 Key Record Dates |
| Last Update Posted: | May 14, 2018 |
| Last Verified: | May 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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PIK3CA mutation advanced solid tumor breast cancer ovarian cancer cancers with a mass |
bulky tumor nodule lump advanced cancer advanced solid malignancies |
Additional relevant MeSH terms:
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Neoplasms Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |