APG-115 in Salivary Gland Cancer Trial
- Interventional
- Recruiting
- NCT03781986
Contact Information
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).
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
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
- 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