Phase Ib Study of Alpelisib With Cisplatin in Patients With HPV+ Solid Tumor Malignancies

NCT02620839 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 159516NCI-2017-01680
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the best dose and side effects of alpelisib and cisplatin in treating patients with human papillomavirus (HPV) positive solid tumor malignancies. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving alpelisib and cisplatin may work better in treating patients with solid tumor malignancies.

Conditions

Solid Tumors

Keywords

CDKN2A-p16 Positive; Locally Advanced Solid Neoplasm; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximally tolerated dose of alpelisib in combination with cisplatin, based upon evaluation of dose-limiting toxicities and adverse events

  Measured using CTCAE v.4.03

  Up to 21 days

• Recommended phase 2 dose of alpelisib in combination with cisplatin, based upon evaluation of dose-limiting toxicities

  Measured using CTCAE v.4.03

  Up to 30 days after the last administration of the study treatment

Secondary Outcomes (4)

• Objective Response Rate

  Up to 30 days after the last administration of the study treatment

• Median duration of response

  Up to 30 days after the last administration of the study treatment

• Median Progression-Free Survival

  Up to 30 days after the last administration of the study treatment

• Incidence of adverse events of the treatment combination

  Up to 30 days after the last administration of the study treatment

Study Arms (7)

Cohort 1A

EXPERIMENTAL

Alpelisib: 200 mg/day, orally, days 1-21 Cisplatin: 30 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 2A

EXPERIMENTAL

Alpelisib: 250 mg/day, orally, days 1-21 Cisplatin: 30 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 2B

EXPERIMENTAL

Alpelisib: 250 mg/day, orally, days 1-21 Cisplatin: 35 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 3A

EXPERIMENTAL

Alpelisib: 300 mg/day, orally, days 1-21 Cisplatin: 30 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 3B

EXPERIMENTAL

Alpelisib: 300 mg/day, orally, days 1-21 Cisplatin: 35 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 4A

EXPERIMENTAL

Alpelisib: 350 mg/day, orally, days 1-21 Cisplatin: 30 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Cohort 4B

EXPERIMENTAL

Alpelisib: 350 mg/day, orally, days 1-21 Cisplatin: 35 mg/m\^2, intravenously, days 1, 8, 15

Drug: Alpelisib; Drug: Cisplatin

Interventions

Alpelisib DRUG

Given PO

Cohort 1A; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 4B

Cisplatin DRUG

Given IV

Cohort 1A; Cohort 2A; Cohort 2B; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 4B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign the informed consent form, and able to comply with the study visit schedule and other protocol requirements. Written informed consent obtained prior to any screening procedures.
• Age ≥ 18 years.
• Dose escalation:
• Any locally advanced or metastatic solid tumor malignancy with no curative treatment options available
• Dose expansion:
• HPV-associated locally advanced or metastatic platinum-resistant solid tumor malignancy. HPV positivity defined by positive p16 immunohistochemistry or in-situ hybridization assessment of archival tissue (primary or metastatic) in a CLIA-certified laboratory. Availability of pathology report from CLIA-certified lab demonstrating positive HPV status by p16 IHC or in situ hybridization qualifies for eligibility determination. Analysis of fresh tumor tissue is permitted in cases where archival tissue is not available.
• Platinum resistance defined as prior progression (radiographic or clinical) either during or within 6 months following completion of platinum-based chemotherapy.
• Platinum-based therapy as most recent systemic therapy prior to enrollment allowed but not required
• Patients may have received any number of lines of prior systemic therapy for locally advanced/metastatic disease.
• Eastern Cooperative Oncology Group performance status ≤ 1
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine \< 1.5 x ULN OR Estimated GFR by Cockroft-Gault equation OR 24 hour urine collection ≥ 60 ml/min

You may not qualify if:

• Prior treatment with PI3K-inhibitor.
• Prior known hypersensitivity to any of the excipients of alpelisib.
• Grade ≥ 2 peripheral neuropathy.
• Grade ≥ sensorineural hearing loss.
• Patients with uncontrolled CNS metastatic involvement. However, patients with metastatic CNS tumors may participate in this study if the patient is:
• \> 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable with respect to the CNS tumor at the time of screening
• Not receiving steroid therapy
• Not receiving anti-convulsive medications that were started for brain metastases.
• Patients who have received prior systemic anti-cancer treatment within 4 weeks or 5 half-lives of prior to starting study treatment, whichever is shorter.
• Prior investigational therapy within 4 weeks of start of study treatment.
• Patients who have received radiotherapy ≤ 2 weeks prior to starting study drugs, with exception of palliative radiotherapy, who have not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated.
• Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such procedure.
• Clinically significant cardiac disease or impaired cardiac function, such as:

Sponsors & Collaborators

• Pamela Munster: lead

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143-1711, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Alpelisib; Cisplatin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Pamela Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: December 1, 2016
• Primary Completion: January 28, 2019
• Study Completion: January 28, 2019
• Last Updated: January 10, 2020

Record last verified: 2020-01

Locations

US (1)