Clinical trial NCT01602315
Conditions: Recurrent Head and Neck Squamous Cell Carcinoma Metastatic Head and Neck Squamous Cell Carcinoma
Keywords: BYL719 PI3K inhibitor PIK3CA cetuximab EGFR HNSCC RM HNSCC platinum-based chemotherapy (RM HNSCC) patients resistant or ineligible/intolerant to platinum-based chemotherapy swallowing dysfunction G-tube alpelisib
Sponsor: Novartis Pharmaceuticals
Start date: 2012-11-12; Completion date: 2016-09-16
Enrollment: 179 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed description:

Arms: arm 1: Oral film-coated tablets without swallowing dysfunction. arm 2: Cetuximab in patients naive to cetuximab (phase ll) arm 3: Crushed film-coated (FC) tablets as an oral suspension with swallowing dysfunction. arm 4: BYL719 + cetuximab in patients resistant to cetuximab. BYL719 can be administered as FC whole/crushed only or DT via G-tube in addition, depending on the Phase Ib results arm 5: BYL719 + Cetuximab in Patients naive to cetuximab. BYL719 can be administered as FC whole/crushed only or DT via G-tube in addition, depending on the Phase Ib results arm 6: Dispersible tablet with swallowing dysfunction administered via a gastrostomy tube (G-tube) arm 7: patients received BYL719 at RP2D in combination with cetuximab.
Interventions: intervention 1: BYL719 as film-coated (FC) whole tablets intervention 2: BYL719 as dispersible tablets (DT) intervention 3: cetuximab intervention 4: BYL719 drink suspension
Intervention descriptions: intervention 1: Oral alpha-specific PI3K inhibitor intervention 2: New formulation of the oral alpha-specific PI3K inhibitor intervention 3: Recombinant chimeric monoclonal antibody driven against EGFR intervention 4: Oral alpha-specific PI3K inhibitor

Protocol documents: