Clinical trial NCT03781986: APG-115 in Salivary Gland Cancer Trial
Official title: A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Salivary Gland Cancer
Salivary Gland Cancer
Keywords: p53 wild-type
Adenoid cystic carcinoma
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Ascentage Pharma Group Inc.
First posted: 2018-12-20
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 -- Parallel assignment \[terminated early\]:

* Arm A: APG-115 Monotherapy
* Arm B: APG-115 + Carboplatin

Part 2 -- Single arm (Arm A only): APG-115 Monotherapy
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
timeFrame: 42 days
measure: Maximally tolerated dose (MTD)
timeFrame: 42 days
measure: Overall response rate
timeFrame: up to 12 months
Secondary outcomes:
measure: Overall response rate by tumor histology
timeFrame: Until death or end of study; up to approximately 5 years
measure: Duration of response
timeFrame: Until death or end of study; up to approximately 5 years
measure: Progression-free survival
timeFrame: Until death or end of study; up to approximately 5 years
measure: Overall survival
timeFrame: Until death or end of study; up to approximately 5 years
measure: Disease control rate
timeFrame: Until death or end of study; up to approximately 5 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Paul L Swiecicki, MD
role: PRINCIPAL_INVESTIGATOR
References: