Clinical trial NCT03795610: Window of Opportunity Study of IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
Head and Neck Carcinoma
Head and Neck Cancer Stage IV
Head and Neck Cancer Stage III
HPV-Related Carcinoma
HPV-Related Malignancy
HPV-Related Squamous Cell Carcinoma
Keywords: HPV positive
HPV negative
HPV-
HPV+
PI3K-γ
microenvironment
immunotherapy
tumor
resection
PI3K
cancer
carcinoma
malignancy
head
neck
throat
esophageal
nasopharyngeal
nasopharynx
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: The V Foundation for Cancer Research
First posted: 2019-01-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: PI3K-y changes
timeFrame: 2 years
Secondary outcomes:
measure: Changes of Myeloid composition
timeFrame: 2 years
measure: changes in T cell composition
timeFrame: 2 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 2 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Ezra Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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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.