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

Primary Purpose

Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Head and Neck Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

IPI-549

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring HPV positive, HPV negative, HPV-, HPV+, PI3K-γ, microenvironment, immunotherapy, tumor, resection, PI3K, cancer, carcinoma, malignancy, head, neck, throat, esophageal, nasopharyngeal, nasopharynx

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UC San Diego Moores Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A: IPI-549 40 mg PO qdaily

Arm Description

Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days

Outcomes

Primary Outcome Measures

PI3K-y changes

To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.

Secondary Outcome Measures

Changes of Myeloid composition

Compare pre- vs. post-treatment tumor tissue

changes in T cell composition

T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.

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

Full Information

NCT ID

NCT03795610

First Posted

December 21, 2018

Last Updated

March 8, 2023

Sponsor

Ezra Cohen

Collaborators

The V Foundation for Cancer Research

1. Study Identification

Unique Protocol Identification Number

NCT03795610

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 6, 2020 (Actual)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ezra Cohen

Collaborators

The V Foundation for Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A: IPI-549 40 mg PO qdaily

Arm Type

Experimental

Arm Description

Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days

Intervention Type

Drug

Intervention Name(s)

IPI-549

Intervention Description

40mg by mouth (PO) every day (QD) for at least 14 days

Primary Outcome Measure Information:

Title

PI3K-y changes

Description

To detect IPI-549-induced changes in PI3Kγ-regulated signatures of immune suppression.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Changes of Myeloid composition

Description

Compare pre- vs. post-treatment tumor tissue

Time Frame

2 years

Title

changes in T cell composition

Description

T cell receptor (TCR) sequencing at baseline, surgery, end of treatment or at time of disease progression.

Time Frame

2 years

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Description

To determine safety and tolerability of IPI-549 and change in tumor size in patients with locally advanced HNSCC

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Debanjali Ghosh, MA

Phone

858-246-0357

d1ghosh@health.ucsd.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Elaine Eng

e1eng@ucsd.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ezra Cohen, MD

Organizational Affiliation

University of California, San Diego

Official's Role

Principal Investigator

Facility Information:

Facility Name

UC San Diego Moores Cancer Center

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Citations:

PubMed Identifier

27179037

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.

Results Reference

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PubMed Identifier

27642729

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.

Results Reference

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PubMed Identifier

23518347

Citation

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.

Results Reference

background

PubMed Identifier

22437938

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.

Results Reference

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PubMed Identifier

21665146

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.

Results Reference

background

PubMed Identifier

19097774

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.

Results Reference

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

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