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A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01708161
Recruitment Status : Terminated
First Posted : October 16, 2012
Results First Posted : June 28, 2018
Last Update Posted : September 13, 2018
Sponsor:
Collaborator:
NantCell, Inc.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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. 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.

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) - Phase Ib [ Time Frame: 28 days ]
    Phase lb only

  2. Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II [ Time Frame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015) ]

    The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

    Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.



Secondary Outcome Measures :
  1. Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib [ Time Frame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013) ]
    The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

  2. Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib [ Time Frame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013) ]
    The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

  3. Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II [ Time Frame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015) ]

    the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

    Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter


  4. Cmax of BYL - Phase Ib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 ]

    Serum concentration for BYL719 (alpelisib)

    1 cycle - 28 days of treatment


  5. Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib [ Time Frame: Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose) ]

    Area under curve for BYL719 (alpelisib)

    1 cycle - 28 days of treatment


  6. Tmax and T Half of BYL - Phase Ib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 ]

    Tmax and half life of BYL719 (Alpelisib)

    1 cycle - 28 days of treatment


  7. Cmax of AMG - Phase Ib [ Time Frame: Cycle 1 Day 15 ]

    Serum concentration for AMG 479 (ganitumab)

    1 cycle - 28 days of treatment


  8. Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib [ Time Frame: Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose) ]

    Area under curve for AMG 479 (ganitumab)

    1 cycle - 28 days of treatment


  9. Tmax and T Half of AMG - Phase Ib [ Time Frame: Cycle 1 Day 15 ]

    Tmax and half life of AMG 479 (ganitumab)

    1 cycle - 28 days of treatment




Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Novartis Pharmaceuticals
NantCell, Inc.
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01708161    
Other Study ID Numbers: CBYL719X2105J
2012-001962-13 ( EudraCT Number )
First Posted: October 16, 2012    Key Record Dates
Results First Posted: June 28, 2018
Last Update Posted: September 13, 2018
Last Verified: August 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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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