NCT03781986

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).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P50-P75 for phase_1

Timeline
8mo left

Started Oct 2019

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress91%
Oct 2019Jan 2027

First Submitted

Initial submission to the registry

December 6, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

December 20, 2018

Completed
10 months until next milestone

Study Start

First participant enrolled

October 28, 2019

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

March 3, 2026

Status Verified

March 1, 2026

Enrollment Period

6.7 years

First QC Date

December 6, 2018

Last Update Submit

March 2, 2026

Conditions

Malignant Salivary Gland CancerSalivary Gland Cancer

Keywords

p53 wild-typeAdenoid cystic carcinoma

Outcome Measures

Primary Outcomes (3)

  • 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

  • Maximally tolerated dose (MTD)

    MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.

    42 days

  • 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 Outcomes (5)

  • Overall response rate by tumor histology

    Until death or end of study; up to approximately 5 years

  • Duration of response

    Until death or end of study; up to approximately 5 years

  • Progression-free survival

    Until death or end of study; up to approximately 5 years

  • Overall survival

    Until death or end of study; up to approximately 5 years

  • Disease control rate

    Until death or end of study; up to approximately 5 years

Study Arms (2)

APG-115 monotherapy

EXPERIMENTAL

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

Drug: APG-115

APG-115 + Carboplatin [terminated]

EXPERIMENTAL

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

Drug: APG-115Drug: Carboplatin

Interventions

APG-115DRUG

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.

APG-115 + Carboplatin [terminated]APG-115 monotherapy
CarboplatinDRUG

Carboplatin is given IV at AUC=4.5 on day 1 of each cycle. Cycle length 21 days.

APG-115 + Carboplatin [terminated]

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Salivary Gland NeoplasmsCarcinoma, Adenoid Cystic

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Mouth NeoplasmsHead and Neck NeoplasmsNeoplasms by SiteNeoplasmsMouth DiseasesStomatognathic DiseasesSalivary Gland DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic Chemicals

Study Officials

  • Paul L Swiecicki, MD

    University of Michigan Rogel Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 6, 2018

First Posted

December 20, 2018

Study Start

October 28, 2019

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

January 1, 2027

Last Updated

March 3, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

US(3)