Cetuximab, Cisplatin and BYL719 for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

NCT02298595 | Withdrawn Phase 1 DMC

• 2 other identifiers: 14-057CBYL719XUS08T
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates the combination of BYL719, cisplatin and cetuximab as induction chemotherapy prior to minimally-invasive transoral surgery (TORS or TLM) and selective lymph node dissection (SLND), followed by risk-adapted intensity-modulated radiation therapy (IMRT) in patients with transorally resectable, Stage III-IVa, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Conditions

Carcinoma, Squamous; Squamous Cell Carcinoma; Oropharyngeal Neoplasms; Oropharyngeal Cancer

Keywords

Carcinoma; Squamous; Oropharyngeal; HPV; Resectable

Outcome Measures

Primary Outcomes (1)

• Complete clinico-radiologic response of primary tumor following induction therapy

  10-11 weeks

Secondary Outcomes (5)

• Pathologic response of primary tumor and lymph nodes following induction therapy

  16-19 weeks

• 2 year recurrence-free survival

  2 years

• Duration of survival

  5 years

• Proportion of patients with genomic PI3K pathway activation who have a complete clinico-radiologic and/or pathologic response to induction therapy

  10-13 weeks

• Number of participants with adverse events

  10-13 weeks

Study Arms (3)

1: Low risk

EXPERIMENTAL

3 cycles (3 weeks) of induction chemotherapy (cisplatin+paclitaxel+BYL719) followed by transoral resection (TORS or TLM) and then observation.

Drug: cisplatin; Drug: Cetuximab; Drug: BYL719

2: Intermediate risk

EXPERIMENTAL

3 cycles (3 weeks) of induction chemotherapy (cisplatin+paclitaxel+BYL719) followed by transoral resection (TORS or TLM) and then Intensity Modulated Radiation Therapy (IMRT).

Drug: cisplatin; Drug: Cetuximab; Drug: BYL719

3: High risk

EXPERIMENTAL

3 cycles (3 weeks) of induction chemotherapy (cisplatin+paclitaxel+BYL719) followed by transoral resection (TORS or TLM) and then Intensity Modulated Radiation Therapy (IMRT) + cisplatin.

Drug: cisplatin; Drug: Cetuximab; Drug: BYL719

Interventions

cisplatin DRUG

75 mg/m2 IV day 1 of each cycle

Also known as: Platinol, Cisplatinum

1: Low risk; 2: Intermediate risk; 3: High risk

Cetuximab DRUG

XXXX day 1, 8, and 15 of each cycle

1: Low risk; 2: Intermediate risk; 3: High risk

BYL719 DRUG

200, 250, 300, or 350 mg/day by mouth every day

1: Low risk; 2: Intermediate risk; 3: High risk

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, cytologically or histologically confirmed squamous cell carcinoma (and common variants, including poorly differentiated carcinoma; undifferentiated carcinoma; basaloid carcinoma) of the oropharynx. Patients must have resectable oropharyngeal and nodal disease, including the following stages according to the American Joint Commission on Cancer Staging 7th edition:
• T1N1-3
• T2N1-3
• T3N0-3
• T4aN0-3. Note: Eligible T4a tumors may include deep/extrinsic tongue muscle invasion and must be judged resectable by TLM or TORS, according to the surgeon-investigator. Patients with T4a tumors with clear radiologic mandibular, hard palate or medial pterygoid invasion are not eligible.
• Carcinoma must be HPV-associated, which is defined as positive for p16 protein by immunohistochemistry (IHC). p16 positivity is defined as ≥70% of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p16 by immunohistochemistry in a CLIA certified pathology lab. p16 testing is standard at participating institutions and may be conducted locally.
• No evidence of distant metastatic disease
• Patients must have a clinically measurable primary oropharyngeal tumor, defined as measuring ≥ 1 cm by spiral CT, per RECIST 1.1, and/or by clinical examination.
• No prior systemic chemotherapy, systemic biologic/molecular targeted therapy or radiation treatment for head and neck cancer.
• Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed without evidence of recurrence.
• Patients must be untreated with radiation above the clavicles.
• Patients with a history of curatively-treated non-HNSCC malignancy must be disease-free for at least 2 years except for excised and cured: carcinoma-in-situ of breast or cervix; non-melanomatous skin cancer; T1-2, N0, M0 resected differentiated thyroid carcinoma; superficial bladder cancer; T1a or T1b prostate cancer comprising \< 5% of resected tissue with normal prostate specific antigen (PSA) since resection.
• Age ≥ 18 years
• Patient has signed the Informed Consent Form (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements
• Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 that the investigator believes is stable at the time of screening

You may not qualify if:

• Patient with poorly controlled diabetes mellitus, defined as FPG \> 140 mg/dL or 7.8 mmol/L
• Patient has a history of another malignancy within 2 years prior to starting study treatment, except for excised and cured: carcinoma-in-situ of breast or cervix; non-melanomatous skin cancer; T1-2, N0, M0 differentiated thyroid carcinoma; superficial bladder cancer; T1a or T1b prostate cancer comprising \< 5% of resected tissue with normal PSA since resection.
• The presence of distant metastatic disease
• Prior systemic chemotherapy, molecularly targeted therapy, or radiation therapy for the current OPSCC diagnosis
• History of radiation to the head and neck (above the clavicles)
• Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure.
• Patient has clinically significant cardiac disease or impaired cardiac function, such as:
• Congestive heart failure (CHF) requiring treatment (New York Heart Association (NYHA) Grade ≥ 2), left ventricular ejection fraction (LVEF) \< 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)
• 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 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
• Patient who has any severe and/or uncontrolled medical conditions such as:
• Active or uncontrolled severe infection requiring systemic antibiotics or antifungals
• Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
• Known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air),

Sponsors & Collaborators

• Julie E. Bauman, MD, MPH: lead
• Novartis: collaborator

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Carcinoma

Interventions

Cisplatin; Cetuximab; Alpelisib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Julie E Bauman, MD, MPH

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: November 24, 2014
• Study Start: August 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2024
• Last Updated: November 13, 2017

Record last verified: 2017-11