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APG-115 in Salivary Gland Cancer Trial

Primary Purpose

Malignant Salivary Gland Cancer, Salivary Gland Cancer

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

APG-115

Carboplatin

About this trial

This is an interventional treatment trial for Malignant Salivary Gland Cancer focused on measuring p53 wild-type, Adenoid cystic carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Moffitt Cancer CenterRecruiting
University of Chicago
University of Michigan Rogel Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

APG-115 monotherapy

APG-115 + Carboplatin [terminated]

Arm Description

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

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.]

Outcomes

Primary Outcome Measures

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

Maximally tolerated dose (MTD)

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

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.

Secondary Outcome Measures

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)

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.

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.

Overall survival

Overall survival (OS) is defined as the duration of time from start of treatment to time of death or end of study.

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

Full Information

NCT ID

NCT03781986

First Posted

December 6, 2018

Last Updated

April 5, 2023

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Ascentage Pharma Group Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03781986

Brief Title

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 28, 2019 (Actual)

Primary Completion Date

July 2024 (Anticipated)

Study Completion Date

January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Ascentage Pharma Group Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Salivary Gland Cancer, Salivary Gland Cancer

Keywords

p53 wild-type, Adenoid cystic carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

APG-115 monotherapy

Arm Type

Experimental

Arm Description

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

Arm Title

APG-115 + Carboplatin [terminated]

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

APG-115

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

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

Primary Outcome Measure Information:

Title

Primary Toxicity Endpoint: dose-limiting toxicity (DLT)

Description

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

Time Frame

42 days

Title

Maximally tolerated dose (MTD)

Description

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

Time Frame

42 days

Title

Overall response rate

Description

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.

Time Frame

up to 12 months

Secondary Outcome Measure Information:

Title

Overall response rate by tumor histology

Description

Time Frame