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Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

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Neoplasms, Squamous Cell

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Carboplatin

Phosphoinositide-3 Kinase Inhibitors

Enzyme Inhibitors

Pyruvate

Patients with advanced solid tumors will be adminsitered Alpelisib and Carboplatin in 21 day cycles until unacceptable toxicity, disease progression or death. At baseline, patients will undergo cross-sectional imaging of the abdomen with HP13C. Participants will wear a glucose monitor for the first two treatment cycles.

Patients with HPV+ squamous cell carcinoma will be administered the recommended phase 2 dose of Alpelisib and Carboplatin in 21 day cycles until unacceptable toxicity, disease progression or death. At baseline, patients will undergo cross-sectional imaging of the abdomen with HP13C. Participants will wear a glucose monitor for the first two treatment cycles

Alpelisib

Hyperpolarized Carbon-13 (13C) Pyruvate

Self-applied devices that sit partially beneath the skin

Continuous Glucose Monitor (CGM)

Pamela Munster, MD

This phase I/II trial tests the safety, side effects, and best dose of alpelisib and whether alpelisib and carboplatin work to shrink tumors in patients with solid tumors or human papillomavirus (HPV) positive squamous cell carcinoma that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Alpelisib belongs to a group of medicines called phosphatidylinositol 3-kinase (PI3K) inhibitors. This means alpelisib blocks the activity of the PI3K protein. The PI3K pathway is well known to be involved in tumor cell multiplication and survival. Blocking PI3K may reduce the ability of certain cancers to grow. Carboplatin is an anticancer drug or chemotherapy drug that binds to DNA causing damage that prevents the DNA from replicating, which prevents the cells itself from reproducing. Giving alpelisib and carboplatin may help control the disease in patients with solid tumors and HPV positive squamous cell carcinoma.

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose and recommended phase 2 dose of alpelisib in combination with carboplatin.

II. To characterize the safety profile of the combination of alpelisib and carboplatin.

III. To determine the overall response rate with the treatment combination in HPV+ solid tumor malignancies (dose expansion).

SECONDARY OBJECTIVES:

I. To determine the median progression-free survival with the treatment combination in HPV+ solid tumor malignancies.

II. To characterize the glycemic impact of the combination of alpelisib and carboplatin.

EXPLORATORY (CORRELATIVE) OBJECTIVES:

I. To investigate the relationship between hyperpolarized carbon-13 with PI3K pathway modulation serially in real time.

II. To measure the prevalence of PIK3CA mutations in the study population.

OUTLINE: This is a phase I, dose-escalation study of alpelisib followed by a phase II dose expansion study. Patients receive alpelisib orally (PO) once daily (QD) on days 1-21 and carboplatin intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Alpelisib in Combination With Carboplatin in Patients With Solid Tumors and HPV-Positive Squamous Cell Carcinoma

A Phase I/II Open-Label Study of Alpelisib (BYL719) in Combination With Carboplatin in Patients With Solid Tumors and HPV+ Squamous Cell Carcinoma

During dose escalation, two dose levels of carboplatin will be evaluated in combination with escalating doses of alpelisib in parallel. The MTD is defined as the highest combination drug dosage not causing dose-limiting toxicities (DLT) in 33% or more of the treated patients in the first 21-day cycle of treatment.

The recommended phase 2 dose will be determined during interim analysis on toxicities reported in Phase 1, and implemented during enrollment of the phase 2 cohort.

Toxicity will be assessed using the NCI CTCAE, version 5.0 unless otherwise specified. A DLT is defined as an AE or abnormal laboratory value assessed as at least possibly related to the study medication, which occurs \<= 21 days following the first dose of alpelisib in combination with carboplatin (Cycle 1).

Percentage of participants with Grade 3 and higher adverse events classified using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5 will be reported.

Overall response rate (ORR) will be reported for the Phase 2 cohort and defined as the number of patients with complete response (CR) or partial response (PR) using RECIST version 1.1 criteria over the total number of patients enrolled in this study. The proportion and corresponding two-sided 90% confidence interval will be reported.

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first for the Phase 2 cohort

Blood glucose will be monitored continuously (every 5 minutes) during treatment using a continuous glucose monitor to characterize the ongoing glycemic impact of alpelisib. Descriptive statistics will be reported for the continuous glucose monitoring (CGM) as the proportion of participants with abnormal glucose levels over time.

Spots Global Cancer Trial Database for continuous glucose monitor (cgm)