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A clinical study with BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma

Phase 1
Conditions
Head and Neck Carcinoma
Registration Number
EUCTR2011-006017-34-FR
Lead Sponsor
ovartis Pharma Services AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
112
Inclusion Criteria

- Age = 18 years
- Patients with histologically/cytologically-confirmed HNSCC
- Patients must be resistant to platinum-based chemotherapy, or be ineligible or intolerant to platinum-based therapy per medical history
- For Phase Ib only, at least 1 prior therapy for recurrent or metastatic disease
- For Phase II only, a maximum of 1 prior therapy for recurrent or metastatic disease
- Prior cetuximab or another EGFR-targeted antibody therapy is allowed only if administered in the induction setting, or concurrently with radiation in the curative setting, with the last dose of cetuximab administered at least 12 months prior to starting the study treatment
- Availability of a representative tumor specimen (primary or metastatic, archival or fresh)
- At least one measurable or non-measurable (as per RECIST 1.1 criteria) lesion is required for patients enrolled in Phase Ib. Measurable disease as determined by RECIST v1.1 is required for Phase II patients.
- World Health Organization (WHO) Performance Status (PS) = 2.
- Adequate organ function and laboratory parameters
- Negative serum pregnancy test

Other inclusion criteria may apply as per protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Prior treatment with PI3K-inhibitors
- Patients with a prior serious infusion reaction to cetuximab
- Patients with primary central nervous system (CNS) tumor or CNS tumor involvement
- Clinically significant cardiac disease or impaired cardiac function
- Patients with diabetes mellitus
- History of another malignancy within 2 years prior to starting study treatment
- Pregnant or nursing (lactating) women

Other exclusion criteria may apply as per protocol

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Phase Ib : To estimate the MTD(s) and/or RP2D of BYL719 in combination with cetuximab in patients with RM HNSCC <br>Phase II : To assess the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients <br>;Secondary Objective: Phase Ib + II<br>To characterize the safety and tolerability of BYL719 in combination with cetuximab<br>To determine the single and multiple dose PK profile of BYL719 in combination with cetuximab<br><br><br>Phase Ib : To assess the preliminary anti-tumor activity of BYL719 in combination with cetuximab <br><br>Phase II : To further assess the anti-tumor activity of the BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients <br>;Primary end point(s): Ph Ib : incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (Cycle 1=28 days)<br>Ph II : Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: approximately 6 months
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Ph Ib and II : <br>Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs) <br>plasma concentration vs. time profiles, plasma PK parameters of BYL719<br>Dose interruptions, reductions and dose intensity<br><br>Ph Ib : <br>overall response rate (ORR) as per RECIST 1.1<br>Disease Control Rate (DCR) as per RECIST 1.1<br>PFS as per RECIST v1.1<br><br>Ph II : <br>1) ORR as per RECIST 1.1<br>2) DCR as per RECIST v1.1 <br>3) overall survival (OS)<br>4) overall survival rate at 6 months (OS6);Timepoint(s) of evaluation of this end point: Ph Ib and II : <br>approximately 6 months for all<br><br>Ph Ib :<br>approximately 6 months for all<br><br>Ph II : <br>1) approximately 6 months<br>2) approximately 6 months<br>3) approximately 1 year<br>4) 6 months
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