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A Study of APG-115 in Patients With Salivary Gland Carcinoma

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ClinicalTrials.gov Identifier: NCT03781986
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : May 28, 2021
Sponsor:
Collaborator:
University of Michigan
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Tracking Information
First Submitted Date  ICMJE December 6, 2018
First Posted Date  ICMJE December 20, 2018
Last Update Posted Date May 28, 2021
Actual Study Start Date  ICMJE October 22, 2019
Estimated Primary Completion Date September 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Primary Toxicity Endpoint: dose-limiting toxicity (DLT) [ Time Frame: 42 days ]
    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) [ Time Frame: 42 days ]
    MTD will be determined based on DLTs observed during the first 6 weeks (2 cycles) of study treatment.
  • Overall response rate [ Time Frame: up to 12 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of APG-115 in Patients With Salivary Gland Carcinoma
Official Title  ICMJE 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
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 consists of 2 arms, arm A is APG-115 monotherapy 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 (APG-115 alone) or Arm B (APG-115 + 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 pharmacokinetic (PK) data will also be considered. After an arm has been chosen to advance an additional 20 patients will be accrued.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part 1:

Arm A: APG-115 Monotherapy, APG-115 (PO): dose= 150 mg, Cycle length: 21 days

Arm B: APG-115 + Carboplatin, APG-115 (PO): dose= 150 mg, Cycle length: 21 days

Carboplatin (IV): dose= AUC 4.5, day= 1, cycle length: 21 days

Part 2:

One of the regimens in Arm A or Arm B based on emerging data from Part 1.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Salivary Gland Cancer
  • Salivary Gland Cancer
Intervention  ICMJE
  • Drug: APG-115
    APG-115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days.
  • Drug: Carboplatin
    Carboplatin is given IV at AUC=4.5. Cycle length 21 days.
Study Arms  ICMJE
  • Experimental: APG-115 monotherapy
    APG-115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days
    Intervention: Drug: APG-115
  • Experimental: APG-115 + Carboplatin
    APG-115 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.
    Interventions:
    • Drug: APG-115
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 18, 2018)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2022
Estimated Primary Completion Date September 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically documented high grade 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
  • 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 breast-feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paul L Swiecicki, MD 734-647-1017 pswiecic@med.umich.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03781986
Other Study ID Numbers  ICMJE APG-115SG101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ascentage Pharma Group Inc.
Study Sponsor  ICMJE Ascentage Pharma Group Inc.
Collaborators  ICMJE University of Michigan
Investigators  ICMJE
Study Chair: Yifan Zhai, MD, PhD Ascentage Pharma Group Inc.
PRS Account Ascentage Pharma Group Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP