Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Head and Neck Cancer Clinical Trial

Official title:

Phase 2 Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03795610
• Other study ID #: 172058
• Status: Recruiting
• Phase: Phase 2
• Start date: March 6, 2020
• Est. completion date: June 2023

Study information

• Verified date: March 2023
• Source: University of California, San Diego
• Contact: Debanjali Ghosh, MA
• Phone: 858-246-0357
• Email: d1ghosh[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate how effective the study drug IPI-549 is against types of cancers. IPI-549 is considered experimental because it is not approved by the US Food and Drug Administration (FDA) for the treatment of cancer.

Patients will be treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

Description:

This is a phase 2 window of opportunity trial in patients with locally advanced head and neck cancer. A key objective is to provide the first proof that macrophage phenotype switching can be accomplished in humans and lay the groundwork for future trials of this novel approach to immune therapy. Patients who are candidates for surgical resection will be enrolled and treated with 2 weeks of IPI-549, a specific PI3Kγ inhibitor. Tumor tissue for research purposes through core biopsies will be obtained prior to initiation of IPI-549 and at surgery.

The study team hypothesizes that mRNA signatures of immune response will be increased in IPI-549-treated patients. For the efficacy endpoints, RECISTv1.1 will be used.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have locally advanced that is amenable to surgical resection

• Must be able to swallow tablets

• Must be able to undergo a core tumor biopsy.

• Must have adequate organ function.

Exclusion Criteria:

• Diagnosis of cutaneous squamous cell carcinoma (SCC) or Epstein-Barr virus (EBV) related nasopharynx cancer.

• Planned major surgery within 4 weeks prior to initiation of study drug

• Patients treated with chemotherapy, biologic therapy, or other investigational agent within < 28 days of starting study drug

• History of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus (HCV)

• On going treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids

• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g. gastric bypass surgery, gastrectomy)

• Female subjects who are pregnant or breastfeeding

• Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Cancer Stage III
• Head and Neck Cancer Stage IV
• Head and Neck Carcinoma
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma
• HPV-Related Carcinoma
• HPV-Related Malignancy
• HPV-Related Squamous Cell Carcinoma
• Neoplasms
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• IPI-549
40mg by mouth (PO) every day (QD) for at least 14 days

Locations

Country	Name	City	State
United States	UC San Diego Moores Cancer Center	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
Ezra Cohen	The V Foundation for Cancer Research

Country where clinical trial is conducted

United States, 

References & Publications (6)

De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013 Mar 18;23(3):277-86. doi: 10.1016/j.ccr.2013.02.013. — View Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation

Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012 Mar 22;12(4):253-68. doi: 10.1038/nri3175. — View Citation

Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, Schmid MC, Sun P, Mose E, Bouvet M, Lowy AM, Valasek MA, Sasik R, Novelli F, Hirsch E, Varner JA. Macrophage PI3Kgamma Drives Pancreatic Ductal Adenocarcinoma Progression. Cancer Discov. 2016 Aug;6(8):870-85. doi: 10.1158/2159-8290.CD-15-1346. Epub 2016 May 13. — View Citation

Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, Woo G, Nguyen AV, Figueiredo CC, Foubert P, Schmid MC, Pink M, Winkler DG, Rausch M, Palombella VJ, Kutok J, McGovern K, Frazer KA, Wu X, Karin M, Sasik R, Cohen EE, Varner JA. PI3Kgamma is a molecular switch that controls immune suppression. Nature. 2016 Nov 17;539(7629):437-442. doi: 10.1038/nature19834. Epub 2016 Sep 19. Erratum In: Nature. 2017 Feb 2;542(7639):124. — View Citation

Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JR, Song X, Wrasidlo W, Blair SL, Ginsberg MH, Cheresh DA, Hirsch E, Field SJ, Varner JA. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011 Jun 14;19(6):715-27. doi: 10.1016/j.ccr.2011.04.016. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PI3K-y changes	To detect IPI-549-induced changes in PI3K?-regulated signatures of immune suppression.	2 years
Secondary	Changes of Myeloid composition	Compare pre- vs. post-treatment tumor tissue	2 years
Secondary	changes in T cell composition	T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.	2 years
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC	2 years