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
Conditions
Keywords
HPV positive, HPV negative, HPV-, HPV+, PI3K-γ, microenvironment, immunotherapy, tumor, resection, PI3K, cancer, carcinoma, malignancy, head, neck, throat, esophageal, nasopharyngeal, nasopharynx
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.
Interventions
DRUGIPI-549
40mg by mouth (PO) every day (QD) for at least 14 days
Sponsors
The V Foundation for Cancer Research
Assuntina G. Sacco, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Experiencing Adverse Events | 7 weeks | To determine safety and tolerability of IPI-549 in patients with locally advanced HNSCC. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: IPI-549 40 mg PO Qdaily Patients enrolled in Arm A will receive IPI-549 40 mg by mouth daily for at least 14 days
IPI-549: 40mg by mouth (PO) every day (QD) for at least 14 days | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen Failure (Did not meet inclusion/exclusion) | 4 |
| Overall Study | Screen Failure (Unknown) | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Arm A: IPI-549 40 mg PO Qdaily |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 56.2 Years STANDARD_DEVIATION 13.29 |
| Cancer Type Nasal cavity | 1 Participants |
| Cancer Type Oral cavity | 4 Participants |
| Cancer Type Oropharynx | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Participants Experiencing Adverse Events
To determine safety and tolerability of IPI-549 in patients with locally advanced HNSCC.
Time frame: 7 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: IPI-549 40 mg PO Qdaily | Participants Experiencing Adverse Events | 10 Participants |