APG-115 +/- Carboplatin for Salivary Gland Cancer

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

41 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug APG-115 +/- Carboplatin for salivary gland cancer?

Research shows that salivary gland cancers can be sensitive to chemotherapy, with some studies indicating a 50% response rate to certain drug combinations. Carboplatin, a component of the treatment, has been evaluated in combination with other drugs for salivary gland carcinoma, suggesting it may have potential benefits. ^{1 2 3 4 5}

Is the combination of APG-115 and Carboplatin safe for humans?

Carboplatin has been studied in various cancers and is generally considered safe, with moderate bone marrow suppression (reduced blood cell production) as the main side effect. It is important to monitor kidney function, as carboplatin is processed by the kidneys, and to be cautious when used with other drugs that affect the bone marrow. ^{1 2 6 7 8}

What makes the drug APG-115 unique for treating salivary gland cancer?

APG-115 (Alrizomadlin) is unique because it is being studied in combination with carboplatin, a platinum-based drug known for its effectiveness in head and neck cancers, but with less toxicity compared to similar drugs like cisplatin. This combination may offer a novel approach for treating salivary gland cancer, a condition with limited standard treatment options. ^{6 9 10 11 12}

What is the purpose of this 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. 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).

Research Team

Paul Swiecicki

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for salivary gland cancer. [2017]

2. Greece pubmed.ncbi.nlm.nih.gov

Carboplatin and Docetaxel in Patients With Salivary Gland Carcinoma: A Retrospective Study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Outcome and management of rare high-grade "salivary" adenocarcinoma: the important role of adjuvant (chemo)radiotherapy. [2020]

5. England pubmed.ncbi.nlm.nih.gov

A randomised phase II trial of epirubicin and 5-fluorouracil versus cisplatinum in the palliation of advanced and recurrent malignant tumour of the salivary glands. [2019]

6. United States 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. [2017]

7. Ireland pubmed.ncbi.nlm.nih.gov

Treatment outcomes of elderly salivary gland cancer patients undergoing radiotherapy - Results from a large multicenter analysis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma. [2014]

9. Greece pubmed.ncbi.nlm.nih.gov

Comparisons of carboplatin and cisplatin as potentiators of 5-fluorouracil and radiotherapy in the mouse L1210 leukaemia model. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with carboplatin and bleomycin for advanced and recurrent head and neck cancer: a phase II study. [2019]

11. Japan pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]