NCT01602315

A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

A Phase Ib Dose Escalation/Randomized Phase II, Multicenter, Open-label Study of BYL719 in Combination With Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 179 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Three different methods of administration and two different BYL719 formulations were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab: Arm A - film-coated whole tablets were orally administered to patients who were able to swallow the tablets; Arm B - a drinkable suspension prepared from crushed film-coated tablets was administered orally to patients with swallowing dysfunction Arm C - a suspension from a dispersible tablet administered via G-tube, in patients with swallowing dysfunction. Arm C was used to investigate the pharmacokinetics (PK), compared to Arm A (film coated tablet), and safety of the dispersible tablet of the dispersible tablet formulation of BYL719. The Phase II investigated the clinical efficacy of BYL719 and consisted of an open label, randomized Phase II part investigating BYL719 in combination with cetuximab compared to cetuximab alone in patients resistant or intolerant to platinum and naïve to cetuximab (Scheme 1: Arm 1 and Arm 2), and a non-randomized Phase II part Scheme 2: Arm 3. In addition, patients who experienced disease progression in Arm 2 (cetuximab) were allowed to switch to the combination regimen (cross-over, Arm 2B). The safety of the BYL719 in combination with cetuximab was also further characterized in Arms 1, 2B and 3. Patients were treated until progression of disease), unacceptable toxicity, or withdrawal of informed consent, whichever occurred first (except for phase II Arm 2 had the opportunity to crossover to the combination treatment (Arm 2B). In the follow-up period all patients had to complete the safety follow-up assessments within 30 days after the last dose of the study treatment. Patients who did not have disease progression at the time of discontinuation of study treatment were radiologically followed for disease status until disease progression, initiation of subsequent anticancer therapies, or death, whichever occurred first. In addition, all patients enrolled in Phase II were followed for survival.

Conditions

• Recurrent Head and Neck Squamous Cell Carcinoma
• Metastatic Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	BYL719 as film-coated (FC) whole tablets	Oral alpha-specific PI3K inhibitor
DRUG	BYL719 as dispersible tablets (DT)	New formulation of the oral alpha-specific PI3K inhibitor
BIOLOGICAL	cetuximab	Recombinant chimeric monoclonal antibody driven against EGFR
DRUG	BYL719 drink suspension	Oral alpha-specific PI3K inhibitor

Timeline

• Start date: 2012-11-12
• Primary completion: 2016-09-16
• Completion: 2016-09-16
• First posted: 2012-05-18
• Last updated: 2020-12-29
• Results posted: 2018-05-21

Locations

29 sites across 9 countries: United States, Australia, Canada, France, Hong Kong, Netherlands, Singapore, South Korea, Taiwan

Regulatory

• FDA-regulated drug study