Ignite Creation Date:
2025-12-24 @ 2:09 PM
Ignite Modification Date:
2026-01-03 @ 9:31 PM
Study NCT ID:
NCT02298595
Status:
WITHDRAWN
Last Update Posted:
2017-11-13
First Post:
2014-11-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cetuximab, Cisplatin and BYL719 for HPV-Associated Oropharyngeal Squamous Cell Carcinoma
Sponsor:
Julie E. Bauman, MD, MPH
Organization:
Study Overview
Official Title:
A Phase I/II Study of BYL719, Cetuximab, and Cisplatin in Transorally Resectable, HPV-Associated Oropharyngeal Squamous Cell Carcinoma
Status:
WITHDRAWN
Status Verified Date:
2017-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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).
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| CBYL719XUS08T | OTHER | Novartis | View |