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

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ClinicalTrials.gov Identifier: NCT03781986
Recruitment Status : Not yet recruiting
First Posted : December 20, 2018
Last Update Posted : September 18, 2019
Sponsor:
Collaborator:
University of Michigan
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

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 mono-therapy and arm B is APG-115 + Carboplatin;

Part 2 is single arm based on the outcome of part 1


Condition or disease Intervention/treatment Phase
Malignant Salivary Gland Cancer Drug: APG115 mono-therapy Drug: APG115 + Carboplatin Other: Part 2 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
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
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
Estimated Study Start Date : September 25, 2019
Estimated Primary Completion Date : September 15, 2022
Estimated Study Completion Date : December 15, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: APG115 mono-therapy
APG115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days
Drug: APG115 mono-therapy
APG115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days

Drug: APG115 + Carboplatin
APG115 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

Other: Part 2
expansion of arm A OR arm B depending on the outcome of Part 1

Experimental: APG115 + Carboplatin
APG115 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
Drug: APG115 mono-therapy
APG115 at 150mg is taken orally every other day within one hour after food. Cycle length 21 days

Drug: APG115 + Carboplatin
APG115 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

Other: Part 2
expansion of arm A OR arm B depending on the outcome of Part 1




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781986


Contacts
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Contact: Yifan Zhai, MD 240-505-6608 yzhai@ascentagepharma.com
Contact: Paul L Swiecicki, MD 734-647-1017 pswiecic@med.umich.edu

Locations
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United States, Michigan
University of Michigan Comprehensive Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Paul L Swiecicki, MD    734-647-1017    pswiecic@med.umich.edu   
Contact: Kathleen Granlund    734-936-0563    kemarsh@med.umich.edu   
Sponsors and Collaborators
Ascentage Pharma Group Inc.
University of Michigan

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Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT03781986     History of Changes
Other Study ID Numbers: APG-115SG101
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Salivary Gland Neoplasms
Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Carboplatin
Antineoplastic Agents