A Study to Evaluate the Potential Benefit of the Addition of BYL719 to Paclitaxel in the Treatment of Breast Cancer and Head-and-neck Cancer

NCT02051751 | Completed Phase 1

• 1 other identifier: CBYL719Z2101
• Study Type: interventional
• Target: 19
• Locations: 4 countries
• Sites: 5

Brief Summary

Dose escalation part:to determine the highest dose of BYL719 administered on a daily basis when given in combination with weekly paclitaxel Dose escalation part: to confirm the safety and tolerability of the BYL719 and paclitaxel combination

Conditions

Neoplasms, Breast Neoplasms, Head and Neck Neoplasms

Keywords

Solid tumors, Head and neck non squamous cell carcinoma, breast cancer, PI3K inhibitor, BYL719, paclitaxel

Outcome Measures

Primary Outcomes (2)

• Dose escalation : Dose Limiting Toxicity (DLT)

  A dose-limiting toxicity (DLT) is an adverse event or abnormal laboratory value assessed as being unrelated to disease, disease progression, inter-current illness, or concomitant medications, and that occurs within the first cycle of treatment with BYL719 plus paclitaxel and meets any of the pre-defined criteria.

  Cycle 1 (28 days)

• Dose expansion : Number of patients with adverse events as a measure of safety and tolerability

  type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity.

  Screening, every 28 days until 30 days after last dose

Secondary Outcomes (7)

• Dose escalation:Number of patients with adverse events as a measure of safety and tolerability

  Screening, every 28 days until 30 days after last dose

• Dose escalation : BYL719 and Paclitaxel Plasma concentrations

  Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9

• Dose expansion: Clinical benefit Rate in the breast cancer cohort

  Baseline, every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

• Dose expansion: Progression free survival

  Baseline, every 6 weeks (head-and-neck squamous cell carcinoma (HNSCC) patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

• Dose expansion: Overall response rate

  Baseline, every 6 weeks (HNSCC patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years

Study Arms (1)

BYL719 and paclitaxel

EXPERIMENTAL

All patients enrolled in the study will receive BYL719 once daily plus weekly paclitaxel

Drug: BYL719; Drug: Paclitaxel

Interventions

BYL719 DRUG

BYL719 will be administered orally once daily on a continuous dosing schedule and dosed on a flat-fixed dose and not adjusted by body weight or body surface area, starting on Day 2 in the dose escalation part and Day 1 in the dose expansion part. In the dose escalation part, the BYL719 starting dose will be 300mg, with anticipated dose escalation to 350mg. In the dose expansion part, BYL719 will be administered at the recommended dose determined in the dose escalation part.

BYL719 and paclitaxel

Paclitaxel DRUG

Paclitaxel will be administered once weekly at a dose of 80 mg/m2 i.v. (days 1, 8, 15 and 22) in a 28 day cycle in both dose escalation and expansion.

BYL719 and paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Adult \> or = 18 years old
• \- has signed the Informed Consent Form (ICF)
• \- has at least one measurable or non-measurable disease as per RECIST 1.1
• \- has tumor tissue available for the analysis as described in the protocol
• \- has adequate bone marrow and organ function as defined in the protocol
• \- is able to swallow and retain oral medication for the dose escalation part, ALL above PLUS
• \- has a histologically-confirmed, advanced unresectable solid tumors who have progressed on standard therapy (or not been able to tolerate) within three months before screening/baseline visit or for whom no standard anticancer therapy exists.
• \- has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 For dose expansion part, patient has ALL of above first six criteria PLUS either: 9- has a histologically/cytologically-confirmed HNSCC as detailed in the protocol and an ECOG performance status ≤ 1 or:
• Patient is a Female with a histologically and/or cytologically confirmed diagnosis of breast cancer as detailed in the protocol and an ECOG performance status ≤ 1

You may not qualify if:

• \- has received previous treatment with a PI3K or AKT inhibitor as described in the protocol
• \- has a known hypersensitivity to paclitaxel or other products containing Cremophor
• \- has a contraindication to use the standard pre-treatment for paclitaxel
• \- has a primary central nervous system (CNS) tumor or CNS tumor involvement as detailed in the protocol
• \- has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• \- has received radiotherapy \> or = 4 weeks prior to starting study drugs, with exception of palliative radiotherapy, who has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated
• \- has peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy or higher)
• \- has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
• \- has a clinically significant cardiac disease or impaired cardiac function as detailed in the protocol
• \- is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
• \- has diabetes mellitus requiring insulin treatment and/or with clinical signs
• \- has impaired gastrointestinal (GI) function or GI disease as described in the protocol
• \- has a known positive serology for human immunodeficiency virus (HIV), active Hepatitis B, and/or active Hepatitis C infection
• \- has any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
• \- is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP3A or CYP2C8 as detailed in the protocol

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Horizon Oncology Center BioAdvance

Lafayette, Indiana, 47905, United States

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Publications (1)

• Rodon J, Curigliano G, Delord JP, Harb W, Azaro A, Han Y, Wilke C, Donnet V, Sellami D, Beck T. A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors. Oncotarget. 2018 Aug 3;9(60):31709-31718. doi: 10.18632/oncotarget.25854. eCollection 2018 Aug 3.

  PMID: 30167089 DERIVED

Related Links

• Novartis results database

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms; Head and Neck Neoplasms

Interventions

Alpelisib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

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: January 21, 2014
• First Posted: January 31, 2014
• Study Start: March 5, 2014
• Primary Completion: August 19, 2016
• Study Completion: August 19, 2016
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

US (2); FR (1); IT (1); ES (1)