Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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:
Collaborator:
Amgen
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01708161
First received: September 19, 2012
Last updated: October 31, 2014
Last verified: October 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (initial 28 days of treatment) ] [ Designated as safety issue: Yes ]
    Phase lb only

  • Objective response rate (ORR) [ Time Frame: Baseline, Every 8 weeks during the 6 months immediately following start of treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    As per RECIST 1.1 (phase lb & ll)

  • Number of patients with Adverse Events (AEs) [ Time Frame: baseline, up to 30 weeks ] [ Designated as safety issue: Yes ]
    phase lb & ll

  • Number of patients with Serious Adverse Events (SAEs) [ Time Frame: Baseline, up to 30 weeks ] [ Designated as safety issue: Yes ]
    phase lb & ll

  • Change in hematology and chemistry values [ Time Frame: baseline, up to 30 weeks ] [ Designated as safety issue: Yes ]
    phase lb & ll

  • Change in vital signs [ Time Frame: baseline, up to 30 weeks ] [ Designated as safety issue: Yes ]
    phase lb & ll

  • Change in electrocardiograms (ECGs) [ Time Frame: baseline, up to 30 weeks ] [ Designated as safety issue: Yes ]
    phase lb & ll

  • Plasma/serum concentration versus time profiles [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Phase II only, no survival follow-up after end of treatment plus 30 days


Enrollment: 47
Study Start Date: November 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (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
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. 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

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
New York, New York, United States, 10021
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 2M9
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Madrid, Spain, 28041
Novartis Investigative Site
Madrid, Spain, 28033
Sponsors and Collaborators
Novartis Pharmaceuticals
Amgen
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01708161     History of Changes
Other Study ID Numbers: CBYL719X2105J, 2012-001962-13
Study First Received: September 19, 2012
Last Updated: October 31, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Spain: Spanish Agency for Medicines and Medical Devices

Keywords provided by Novartis:
PIK3CA mutation, advanced solid tumor, breast cancer, ovarian cancer

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014