APG-115 in Salivary Gland Cancer Trial

University of Michigan Rogel Cancer Center

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Salivary Gland Cancer; Malignant Salivary Gland Cancer

Treatments: Drug: Carboplatin; Drug: APG-115

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03781986

APG-115SG101

HUM00155822 (Other Identifier)

UMCC 2018.127

Details and patient eligibility

About

This is a phase I/II trial to evaluate the efficacy of APG-115 +/- Carboplatin for the treatment p53 wild-type malignant salivary gland cancer.

Part 1 consisted of 2 arms, arm A (APG-115 monotherapy) and arm B (APG-115 + Carboplatin) and was terminated early.

Part 2 is a single arm study (APG-115 monotherapy).

Full description

The current single arm study design was originally part of a study with a parallel arm given combination APG-115 + Carboplatin. In the initial phase of that previous iteration, the combination arm was closed early for issues related to tolerability of the combination therapy. This study will continue as a single arm, monotherapy alone, Phase I/II study as approved by the UM Institutional Review Board as of June 2021.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically documented malignant salivary gland cancers (including secretory glands of the aerodigestive tract) with or without metastases, not amenable to curative treatment; or there is documentation of patient refusal of curative treatment.
• Previous mutational testing with no evidence of a p53 mutation
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Presence of measurable disease by CT scan per RECIST v1.1 with ≥ 20% increase in tumor burden in the preceding 12 months
• Life expectancy of ≥12 weeks
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Patients must be able to take oral medication without breaking/opening, crushing, dissolving, or chewing capsules
• Adequate organ and marrow function obtained ≤ 2 weeks prior to enrollment

Exclusion criteria

• Prior treatment with MDM2 inhibitors
• Patients are not eligible if they have received any systemic anti-cancer therapy (including chemotherapy and/or hormone therapy) for salivary gland cancer within 4 weeks of the start of study therapy
• Patients are not eligible if they have received any of the following within 4 weeks of the start of study therapy: live vaccines, antiretroviral drugs
• Progressive disease within 6 months of the last dose of platinum-based chemotherapy
• Patients with active brain metastases are excluded because of unknown penetration into the central nervous system (CNS). A confirmatory scan for asymptomatic patients is not required. Patients with a history of treated CNS metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 4 weeks between completion of radiotherapy and enrollment, and recovery from significant (Grade ≥ 3) acute toxicity.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
• Patients (male and female) having procreative potential who are not willing or not able to use 2 adequate methods of contraception or practicing abstinence during the study and for 90 days following their last dose of treatment
• Women who are pregnant or breast-feeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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41 participants in 2 patient groups

APG-115 monotherapy

Experimental group

Description:

APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.

Treatment:

Drug: APG-115

APG-115 + Carboplatin [terminated]

Experimental group

Description:

APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. \[Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.\]

Treatment:

Drug: APG-115

Drug: Carboplatin