NCT02298595

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

A Phase I/II Study of BYL719, Cetuximab, and Cisplatin in Transorally Resectable, HPV-Associated Oropharyngeal Squamous Cell Carcinoma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Julie E. Bauman, MD, MPH · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

HPV status and tobacco use are the major independent prognostic factors for patients with OPSCC. Patients with HPV-associated OPSCC have a favorable prognosis when treated with chemotherapy, radiation, and/or surgery. This has resulted in national trials investigating de-intensification strategies for good-risk patients with HPV-associated OPSCC, where current multimodality paradigms may represent overtreatment. The PI3K/Akt/mTOR signaling network, a mitogenic pathway regulating cellular metabolism, proliferation and survival, plays a major role in HPV biology. Starting with early infection, activation of PI3K suppresses autophagy and induces functional protein translational machinery. Activation of the pathway is a nearly universal aspect of mammalian viral infection, and is of particular importance for dsDNA viruses such as HPV. The oncoproteins E5, E6 and E7 also have direct roles in pathway activation. Moreover, HPV-associated OPSCC demonstrates a strikingly high prevalence of genomic activation of the PI3K pathway, including activating PIK3CA mutations (27-31%), PIK3CA amplification (20%), and loss of PTEN (30%), the negative regulator of PI3K. Overall genomic events hypothesized to result in PI3K pathway activation are present in approximately 45-60% of HPV-transformed OPSCC. BYL719 is an oral, small molecule, alpha-specific inhibitor of PI3-Kinase. Because HPV-associated OPSCC demonstrates a high rate of both genomic and non-genomic PI3K pathway activation, we hypothesize that adding BYL719 to platinum-taxane induction chemotherapy in HPV-associated OPSCC will increase clinico-radiologic complete response relative to historical control. In this phase I/II trial, eligible patients wiht HPV-associated OPSCC will be treated with 3 cycles of induction BYL719, cisplatin and paclitaxel. Induction will be followed by minimally-invasive, transoral surgery (TORS or TLM) then risk-adapted IMRT.

Conditions

• Carcinoma, Squamous
• Squamous Cell Carcinoma
• Oropharyngeal Neoplasms
• Oropharyngeal Cancer

Interventions

Type	Name	Description
DRUG	cisplatin	75 mg/m2 IV day 1 of each cycle
DRUG	Cetuximab	XXXX day 1, 8, and 15 of each cycle
DRUG	BYL719	200, 250, 300, or 350 mg/day by mouth every day

Timeline

• Start date: 2016-08-01
• Primary completion: 2019-08-01
• Completion: 2024-08-01
• First posted: 2014-11-24
• Last updated: 2017-11-13