Cetuximab + BYL719 + IMRT (Intensity-Modulated Radiation Therapy) in Stage III/IVB Head and Neck Squamous Cell Cancer (HNSCC)

NCT02282371 | Completed Phase 1

• 1 other identifier: 14-116
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief Summary

This is a phase 1b study, which means that the purpose of the study is to establish the maximum dose of a pill drug called BYL719, when given with a standard treatment for patients with head and neck squamous cell cancer.

Conditions

Head and Neck Squamous Cell Cancer

Keywords

Cetuximab; BYL719; IMRT (Intensity-Modulated Radiation Therapy); 14-116

Outcome Measures

Primary Outcomes (1)

• determine the phase II-recommended dose of BYL719

  Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable.

  2 years

Secondary Outcomes (1)

• Adverse events

  2 years

Study Arms (1)

Cetuximab + BYL719 + IMRT

EXPERIMENTAL

Cetuximab loading dose, 400 mg/m2 intravenously (IV). IMRT, 1 fraction/day, up to total of approximately 70 Gy, over approximately 33 treatment days Cetuximab 250 mg/m2 weekly IV X 7 weeks Daily BYL719, according to dose escalation scheme followup clinic visits every 3 months for 2 years,every 6 months for the next 3 years, and annually thereafter.

Drug: Cetuximab; Drug: BYL719; Radiation: IMRT (Intensity-Modulated Radiation Therapy)

Interventions

Cetuximab DRUG

Cetuximab + BYL719 + IMRT

BYL719 DRUG

Cetuximab + BYL719 + IMRT

IMRT (Intensity-Modulated Radiation Therapy) RADIATION

Cetuximab + BYL719 + IMRT

Eligibility Criteria

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

You may qualify if:

• Locally and/or regionally advanced (M0) head and neck squamous cell carcinoma (AJCC Stage III-IVB), cytologically or pathologically confirmed by Department of Pathology at MSKCC, for which curative-intent radiation therapy is planned.
• Age ≥ 18 years
• ECOG Performance Status ≤ 1
• Adequate organ function and laboratory parameters as defined by:
• Absolute neutrophil count ≥ 1.0 x 109/L
• Hemoglobin ≥ 9 g/dl
• Platelets ≥ 100 x 109/L
• AST/SGOT and ALT/SGPT ≤ 2.5X ULN (upper limit of normal)
• bilirubin ≤ 1.5X ULN
• creatinine ≤ 1.5X ULN
• Fasting glucose \< 140 mg/dL
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for males at least 4 months thereafter and for females at least 3 months thereafter.
• Negative serum pregnancy test (β-hCG) within 72 hours before starting study treatment for all women of childbearing potential.
• Able to understand and voluntarily sign the informed consent form, and able to comply with the study visit schedule and other protocol requirements.
• Low risk for tumor lysis syndrome (TLS)

You may not qualify if:

• Any prior known radiation therapy in head and neck area
• Clinically significant cardiac disease or impaired cardiac function such as:
• Congestive heart failure (CHF) requiring treatment (New York Heart Association ≥ grade 2), Left Ventricular Ejection Fraction (LVEF) ≤ 50% dose determined by multi-gated acquisition (MUGA) scan or echocardiogram, or uncontrolled arterial hypertension defined by blood pressure greater than 140/80 mmHg at rest (average of 3 consecutive readings)
• History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, (e.g. congenital long QT syndrome, high grade\\complete AV blockage).
• Acute coronary syndrome (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), for coronary angiography angioplasty and stenting), \< 3 months prior to screening
• QT interval adjusted according to Fredericia (QTcF) \> 480 msec on screening EKG
• Patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus
• Patient with history of another malignancy within 2 years prior to starting study treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
• Patient who has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient who has had systemic therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
• Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
• 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, e.g. infection/inflammation, intestinal obstruction, social/psychological complications
• Impaired GI function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Patient who has participated in a prior therapeutic investigational drug study within 30 days prior to enrollment
• Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (6)

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, 07939, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Cetuximab; Alpelisib; Radiotherapy, Intensity-Modulated

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• David Pfister, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 4, 2014
• Study Start: October 30, 2014
• Primary Completion: October 22, 2021
• Study Completion: October 22, 2021
• Last Updated: October 26, 2021

Record last verified: 2021-10

Locations

US (6)