NCT01708161

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Nov 2012

Longer than P75 for phase_1

Geographic Reach
4 countries

10 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 19, 2012

Completed
27 days until next milestone

First Posted

Study publicly available on registry

October 16, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

November 27, 2012

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 26, 2014

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

June 28, 2018

Completed
Last Updated

September 13, 2018

Status Verified

August 1, 2018

Enrollment Period

2.1 years

First QC Date

September 19, 2012

Results QC Date

May 31, 2018

Last Update Submit

August 15, 2018

Conditions

PIK3CA Mutated Advanced Solid TumorsPIK3CA Amplified Advanced Solid Tumors

Keywords

PIK3CA mutationadvanced solid tumorbreast cancerovarian cancercancers with a massbulky tumornodulelumpadvanced canceradvanced solid malignancies

Outcome Measures

Primary Outcomes (2)

  • Dose Limiting Toxicities (DLTs) - Phase Ib

    Phase lb only

    28 days

  • Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

    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.

    Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

Secondary Outcomes (9)

  • Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib

    Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

  • Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib

    Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

  • Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

    Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

  • Cmax of BYL - Phase Ib

    Cycle 1 Day 1, Cycle 1 Day 15

  • Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib

    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)

  • +4 more secondary outcomes

Study Arms (1)

BYL719 + AMG 479

EXPERIMENTAL

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: BYL719Drug: AMG 479

Interventions

BYL719DRUG

BYL719 is a small molecule inhibiting PI3-Kinase.

Also known as: ALPELISIB
BYL719 + AMG 479
AMG 479DRUG

AMG 479 is a monoclonal antibody directed against IGF1-R.

Also known as: ganitumab
BYL719 + AMG 479

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Novartis Investigative Site

Los Angeles, California, 90095, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

New York, New York, 10017, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28033, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Breast NeoplasmsOvarian Neoplasms

Interventions

Alpelisibganitumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Limitations and Caveats

Due to the competitive landscape for anticancer therapies in ovarian and breast cancer and given the limited clinical activity observed with the study combination treatment, Novartis decided in 2014 to halt the recruitment in the trial.

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
Novartis.email@novartis.com
1-888-669-6682

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 19, 2012

First Posted

October 16, 2012

Study Start

November 27, 2012

Primary Completion

December 26, 2014

Study Completion

June 1, 2017

Last Updated

September 13, 2018

Results First Posted

June 28, 2018

Record last verified: 2018-08

Locations

ES(4)US(4)CA(1)BE(1)