APG-115 +/- Carboplatin for Salivary Gland Cancer

Not currently recruiting at 3 trial locations

Overseen By Paul Swiecicki

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: MDM2 inhibitors, Antiretrovirals, Chemotherapy

Disqualifiers: Active brain metastases, Uncontrolled disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called APG-115, an experimental treatment, to evaluate its effectiveness against a type of salivary gland cancer that hasn't spread and lacks a specific gene mutation (p53 mutation). The research examines whether APG-115 can treat this cancer when used alone. Suitable candidates for this trial have a confirmed diagnosis of malignant salivary gland cancer, have not recently undergone certain treatments, and do not have the specific genetic mutation. Participants must have a tumor that has grown in the last year and be able to take oral medication in capsule form. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had any systemic anti-cancer therapy or certain other treatments within 4 weeks before starting the study. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that APG-115, when used alone, yields promising results and is generally safe for treating a type of salivary gland cancer. In studies, 13% of patients experienced tumor shrinkage, and in 94% of cases, the cancer did not progress, suggesting the drug is usually well-tolerated. However, when combined with Carboplatin, the trial ended early, and a safe dose for this combination was not fully determined. As this research remains in the early stages, information is limited, and the safety of the treatment continues to be studied. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for salivary gland cancer?

Researchers are excited about APG-115 for treating salivary gland cancer because it works differently from standard chemotherapy options like cisplatin or doxorubicin. APG-115 is a new type of drug known as an MDM2 inhibitor, which means it helps reactivate the tumor-suppressing protein p53, potentially stopping cancer cells from growing. In contrast, traditional treatments mainly focus on directly killing cancer cells, often affecting healthy cells, too. This unique approach could lead to more targeted cancer control with possibly fewer side effects.

What evidence suggests that APG-115 might be an effective treatment for salivary gland cancer?

Studies have shown that APG-115, one of the treatments under study in this trial, significantly affects a type of salivary gland cancer with a specific gene called p53 when used alone. Research indicates that 13% of patients experienced tumor shrinkage, and 94% either had their tumors shrink or their cancer stopped growing. These results suggest that APG-115 can help control the cancer in most cases. The safety profile is considered acceptable, as it generally does not cause severe side effects. Overall, these findings highlight its potential as a promising treatment option. ^{1 2 3 5 6}

Who Is on the Research Team?

Paul Swiecicki

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with malignant salivary gland cancer that can't be cured by surgery or other treatments, or they've refused such treatments. They should have no p53 gene mutations, be in good physical condition (ECOG ≤1), and have a life expectancy of at least 12 weeks. Participants must not have had recent cancer therapy and must agree to use two forms of contraception.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

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

I can swallow pills without needing to break or crush them.

Exclusion Criteria

I haven't had any cancer treatment for my salivary gland cancer in the last 4 weeks.

I don't have active brain cancer, but if I had it before, it's treated and stable for at least 4 weeks.

I am not willing or able to use two forms of birth control or abstain for 90 days after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• APG-115
• Carboplatin

Trial Overview The study is testing the effectiveness of APG-115 alone for treating p53 wild-type malignant salivary gland cancer. The first part included an additional arm with APG-115 plus Carboplatin but was stopped early; now it's just focusing on APG-115 as a single agent.

How Is the Trial Designed?

Group I: APG-115 monotherapy Experimental Treatment 1 Intervention

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

Group II: APG-115 + Carboplatin [terminated] Experimental Treatment 2 Interventions

APG-115 and Carboplatin will be administered in an open label fashion until progression, intolerance, or patient preference. \[Phase 1 was terminated early and this arm was discontinued. An MTD was not established during Phase 1.\]

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Ascentage Pharma Group Inc.

Industry Sponsor

Trials

54

Recruited

5,700+

Published Research Related to This Trial

In a study of 31 patients with recurrent or metastatic head and neck cancer, carboplatin showed a 26% response rate (complete or partial responses) with a median duration of 4.5 months, indicating its potential effectiveness against advanced squamous-cell carcinoma.

Carboplatin demonstrated a different toxicity profile compared to cisplatin, with moderate bone marrow suppression being the main side effect, while avoiding nephrotoxicity and allowing for outpatient treatment, making it a safer option for patients with renal concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. Eisenberger, M., Hornedo, J., Silva, H., et al.[2017]

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

Carboplatin (CBDCA) has shown similar effectiveness to cisplatin in treating various cancers, including head and neck and ovarian cancers, while demonstrating significantly lower toxicity, particularly in terms of renal effects and side effects like nausea and vomiting.

In clinical trials, carboplatin's dose-limiting factor was myelosuppression, making it a safer alternative to cisplatin, which has more severe side effects, thus positioning carboplatin as a valuable option in cancer chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. Tsukagoshi, S.[2013]

In a study of 288 elderly patients (≥65 years) with salivary gland cancer undergoing (chemo)radiotherapy, the median local/locoregional control (LRC) was 113 months, indicating favorable oncological outcomes despite the patients' age.

While higher doses of radiotherapy improved local control, they did not enhance progression-free survival (PFS) or overall survival (OS), and moderate toxicities were observed, with 24.3% experiencing acute grade 3 toxicities, suggesting that treatment decisions should prioritize patient performance over age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of elderly salivary gland cancer patients undergoing radiotherapy - Results from a large multicenter analysis. Akbaba, S., Rühle, A., Rothhaar, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03781986

NCT03781986 | APG-115 in Salivary Gland Cancer Trial 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.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624000671

8 Phase I/II Study of A Novel MDM-2 Inhibitor (APG-115- ... A phase 1/2 multicenter study was conducted to evaluate the safety and efficacy of APG-115 +/- carboplatin in p53wt SGC. Eligibility criteria included high ...

3. cancernetwork.com cancernetwork.com/view/apg-115-showcases-early-activity-in-p53-wild-type-salivary-gland-cancer

APG-115 Showcases Early Activity in p53 Wild-Type ... At a median follow-up of 22.1 months, the best response with APG-115 was a partial response (PR) in 13% (n = 4) of patients and stable disease ( ...

4. withpower.com withpower.com/trial/phase-2-salivary-gland-neoplasms-9-2019-70eeb

APG-115 +/- Carboplatin for Salivary Gland Cancer In a study of 31 patients with recurrent or metastatic head and neck cancer, carboplatin showed a 26% response rate (complete or partial responses) with a ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03781986/

Clinical Trial: NCT03781986 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.

6. accrf.org accrf.org/wp-content/uploads/2022/10/APG-115-Triple-Meeting-Poster-101422.pdf

Phase I/II Study of a Novel MDM-2 inhibitor (APG-115/ ... Malignant salivary gland cancers (SGC) are rare tumors of the head and neck with no approved therapeutics. • TP53 mutations seen in approx. 20-30%.