Clinical Trials /

A Phase I/II Trial of APG-115 in Patients With Salivary Gland Carcinoma

NCT03781986

Description:

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 consists of 2 arms, arm A is APG-115 mono-therapy and arm B is APG-115 + Carboplatin; Part 2 is single arm based on the outcome of part 1

Related Conditions:
  • Salivary Gland Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Multicenter Phase I/II Trial of APG-115 in P53 Wild-Type Salivary Gland Carcinoma
  • Official Title: A Multicenter Phase I/II Trial of A Novel MDM2 Inhibitor(APG-115) With or Without Platinum Chemotherapy in P53 Wild-Type Salivary Gland Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: APG-115SG101
  • NCT ID: NCT03781986

Conditions

  • Malignant Salivary Gland Cancer

Interventions

DrugSynonymsArms
APG115 mono-therapyAPG115 mono-therapy
APG115 + CarboplatinAPG115 mono-therapy

Purpose

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 consists of 2 arms, arm A is APG-115 mono-therapy and arm B is APG-115 + Carboplatin; Part 2 is single arm based on the outcome of part 1

Detailed Description

      This is an open label multi-institution phase I/II study with an initial randomized component
      then followed by a planned single-arm phase. Arms will be monitored using the time-to-event
      continual reassessment method (TITE-CRM). In the initial randomized phase, patients will be
      randomized to one of two arms: Arm A (APG115 alone) or Arm B (APG115 + Carboplatin) at a
      ratio of 1:2. After 14 patients have been accrued in Arm A and 28 patients have been accrued
      to Arm B, responses will be tabulated. The outcomes of the arms will be considered, and a
      single arm will be selected for further study in part 2 of the study. Response rate (defined
      as CR or PR after cycle 2) will be the foremost consideration for deciding on the most
      promising arm; in addition, a comprehensive evaluation of the available data including
      toxicity and PK data will also be considered. After an arm has been chosen to advance an
      additional 20 patients will be accrued.
    

Trial Arms

NameTypeDescriptionInterventions
APG115 mono-therapyExperimentalAPG115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days
  • APG115 mono-therapy
  • APG115 + Carboplatin
APG115 + CarboplatinExperimentalAPG115 at 150mg is taken orally every other day within one hour after food. Carboplatin is given IV at AUC=4.5, Cycle length 21 days
  • APG115 mono-therapy
  • APG115 + Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented malignant salivary gland cancers 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.

          -  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.

          -  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 with platinum-based chemotherapy within the last 6 months.

          -  Patients with active brain metastases are excluded because of unknown penetration into
             the CNS. A confirmatory scan for asymptomatic patients is not required. Patients with
             a history of treated central nervous system (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
Time Frame:42 days
Safety Issue:
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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

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