APG-115 in Salivary Gland Cancer Trial

Salivary Gland Cancer Clinical Trial

Official title:

A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03781986
• Other study ID #: UMCC 2018.127
• Secondary ID: APG-115SG101HUM0
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 28, 2019
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignant Salivary Gland Cancer
• Salivary Gland Cancer
• Salivary Gland Neoplasms

Intervention

Drug:
• APG-115
APG-115 at 150mg (or lower, if dose is reduced) is taken orally every other day through day 13 of each cycle. Cycle length 21 days.
• Carboplatin
Carboplatin is given IV at AUC=4.5 on day 1 of each cycle. Cycle length 21 days.

Locations

Country	Name	City	State
United States	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	University of Chicago	Chicago	Illinois
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center	Ascentage Pharma Group Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Toxicity Endpoint: dose-limiting toxicity (DLT)	DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0	42 days
Primary	Maximally tolerated dose (MTD)	MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.	42 days
Primary	Overall response rate	Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR). Response will be assessed via RECIST v1.1.	up to 12 months
Secondary	Overall response rate by tumor histology	Overall response rate will be defined as the proportion of patients achieving either complete response (CR) or partial response (PR), assessed via RECIST v1.1 and reported separately for those with histologically confirmed adenoid cystic carcinoma (ACC) versus other malignant salivary gland tumors (non-ACC)	Until death or end of study; up to approximately 5 years
Secondary	Duration of response	The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started.	Until death or end of study; up to approximately 5 years
Secondary	Progression-free survival	Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever is earlier.	Until death or end of study; up to approximately 5 years
Secondary	Overall survival	Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.	Until death or end of study; up to approximately 5 years
Secondary	Disease control rate	Defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD). Response will be assessed via RECIST v1.1	Until death or end of study; up to approximately 5 years