Clinical trial NCT01708161: A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
Official title: A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: PIK3CA Mutated Advanced Solid Tumors
PIK3CA Amplified Advanced Solid Tumors
Keywords: PIK3CA mutation
advanced solid tumor
breast cancer
ovarian cancer
cancers with a mass
bulky tumor
nodule
lump
advanced cancer
advanced solid malignancies
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: NantCell, Inc.
First posted: 2012-10-16
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) - Phase Ib
timeFrame: 28 days
measure: Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
timeFrame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Secondary outcomes:
measure: Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib
timeFrame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
measure: Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib
timeFrame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
measure: Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
timeFrame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
measure: Cmax of BYL - Phase Ib
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15
measure: Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib
timeFrame: 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)
measure: Tmax and T Half of BYL - Phase Ib
timeFrame: Cycle 1 Day 1, Cycle 1 Day 15
measure: Cmax of AMG - Phase Ib
timeFrame: Cycle 1 Day 15
measure: Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib
timeFrame: Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
measure: Tmax and T Half of AMG - Phase Ib
timeFrame: Cycle 1 Day 15
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: