- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03781986
APG-115 in Salivary Gland Cancer Trial
February 28, 2024 updated by: University of Michigan Rogel Cancer Center
A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma
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).
Study Overview
Status
Suspended
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
34
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Rogel Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: APG-115 monotherapy
APG-115 will be administered in an open label fashion until progression, intolerance, or patient preference.
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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.
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Experimental: APG-115 + Carboplatin [terminated]
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.]
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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 is given IV at AUC=4.5 on day 1 of each cycle.
Cycle length 21 days.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
Time Frame: 42 days
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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
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42 days
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Maximally tolerated dose (MTD)
Time Frame: 42 days
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MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.
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42 days
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Overall response rate
Time Frame: up to 12 months
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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.
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up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate by tumor histology
Time Frame: Until death or end of study; up to approximately 5 years
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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)
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Until death or end of study; up to approximately 5 years
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Duration of response
Time Frame: Until death or end of study; up to approximately 5 years
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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.
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Until death or end of study; up to approximately 5 years
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Progression-free survival
Time Frame: Until death or end of study; up to approximately 5 years
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Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever is earlier.
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Until death or end of study; up to approximately 5 years
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Overall survival
Time Frame: Until death or end of study; up to approximately 5 years
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Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.
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Until death or end of study; up to approximately 5 years
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Disease control rate
Time Frame: Until death or end of study; up to approximately 5 years
|
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
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Until death or end of study; up to approximately 5 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Paul L Swiecicki, MD, University of Michigan Rogel Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 28, 2019
Primary Completion (Estimated)
July 1, 2024
Study Completion (Estimated)
January 1, 2025
Study Registration Dates
First Submitted
December 6, 2018
First Submitted That Met QC Criteria
December 18, 2018
First Posted (Actual)
December 20, 2018
Study Record Updates
Last Update Posted (Actual)
March 1, 2024
Last Update Submitted That Met QC Criteria
February 28, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UMCC 2018.127
- APG-115SG101 (Other Identifier: Ascentage Pharma)
- HUM00155822 (Other Identifier: University of Michigan IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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