An Open Label, Single Arm, Multicenter Phase II Study of BYL719 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck Who Failed to Respond to Platinum-based Therapy.
Overview
- Phase
- Phase 2
- Intervention
- BYL719
- Conditions
- Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck
- Sponsor
- Yonsei University
- Enrollment
- 43
- Locations
- 1
- Primary Endpoint
- Disease control rate
- Last Updated
- 7 years ago
Overview
Brief Summary
One promising approach to the treatment of cancer is inhibition or modulating the crucial signal transduction pathway of PI3K-Akt-mTOR. Several PI3K inhibitors are being tested in the clinical trials for cancer treatment but not for the head and neck cancer yet. BYL719 is an alpha specific I PI3K inhibitor. It showed significant, concentration dependent cell growth inhibition and induction of apoptosis. We suggest multicenter single arm phase II study to determine anti-tumor effects of BYL719 in patients with recurrent and/or metastatic SCCHN who failed to prior chemotherapy regimens. Enrollment will be done in 5 or more clinical trial centers in Korea. Primary objective is to evaluate disease control rate (DCR) at 8 weeks of BYL719, and the efficacy will be evaluated by the investigators analysis based on RECIST version 1.1.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed recurrent or metastatic squamous-cell carcinoma of head and neck (SCCHN), except nasopharyngeal carcinoma
- •18 years of age or older
- •Patients must have progressive disease after one or two prior chemotherapy regimens including platinum-based chemotherapy given for the treatment of recurrent and/or metastatic disease, or within 6 months after concurrent chemoradiation (with or without induction chemotherapy) given as a definitive treatment.
- •Life expectancy of at least 12 weeks
- •Ineligibility for local therapy (surgery or radiation for curative intent)
- •At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or MRI
- •ECOG performance score of 0-2
- •Availability of tissue samples (archival tissue or rebiopsied tissues) for molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
- •Adequate organ function and laboratory parameters as defined by:
- •Absolute neutrophil count (ANC) ≥1.5x109/L
Exclusion Criteria
- •Prior treatment with PI3K pathway inhibitors
- •Nasopharyngeal carcinoma
- •Uncontrolled, untreated brain metastasis. Patients with treated/controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy, should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment).
- •Surgery, chemotherapy or irradiation within 3 weeks of study entry
- •Concomitant chemotherapy, hormonal therapy or immunotherapy
- •Clinically significant cardiac disease or impaired cardiac function, such as:
- •Congestive heart failure (CHF) requiring treatment (New Yort Heart Association (NYHA) Grade ≥ 2), left ventricular ejection fraction (LVEF) \< 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO), or uncontrolled arterial hypertension defined by blood pressure \> 140/100 mmHg at rest (average of 3 consecutive readings)
- •History or current evidence of clinically significant cardiac arrhythmias, arterial fibrillation and/or conduction abnormality, e.g. congenical long QT syndrome, high grade/complete AV-blockage
- •Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), \< 3 months prior to screening
- •QT interval adjusted according to Fredericia (QTcF) \> 480 msec on screening ECG
Arms & Interventions
BYL719
BYL719 is an oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds.
Intervention: BYL719
Outcomes
Primary Outcomes
Disease control rate
Time Frame: 8 weeks of BYL 719 administered as therapy
The primary objective of this study is to evaluate disease control rate (DCR) at 8 weeks of BYL719 administered as therapy for patient with recurrent/metastatic head and neck squamous cell carcinoma, comparing with historical control. Efficacy evaluation will be based on RECIST version 1.1. DCR will be expressed percent and 95% confidence interval.
Secondary Outcomes
- Progression-free survival (PFS)(24 months)
- Overall survival (OS)(24 months)
- Overall Response Rate (ORR)(24 months)
- Time to progression (TPP)(24 months)
- Drug toxicity and safety analysis(24 months)
- Quality of life assessment(24 months)