Targeted Therapy for Salivary Gland Cancer

Overseen By Anna Spreafico

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: QTc prolonging drugs

Disqualifiers: Cardiac illness, Active malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

114 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 use drugs that may prolong the QTc interval (a measure of heart rhythm). It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug for salivary gland cancer?

Research shows that certain proteins like EGFR and HER2 are often present in salivary gland cancers, and targeting these proteins with specific drugs can be effective. For example, anti-androgen therapy has shown promise in treating salivary gland cancers that express androgen receptors, similar to its use in prostate cancer. ^{1 2 3 4 5}

Is the targeted therapy for salivary gland cancer generally safe for humans?

The safety of targeted therapies like EGFR and HER2 inhibitors has been studied in salivary gland cancer, showing that these treatments can be used in humans, but specific safety data for each treatment is not detailed in the provided research. ^{1 2 4 5 6}

How is the drug for salivary gland cancer different from other treatments?

This drug is unique because it targets specific proteins and pathways involved in salivary gland cancer, such as EGFR, HER2, and androgen receptors, which are not effectively addressed by standard chemotherapy. It includes a combination of inhibitors that block these proteins, potentially offering a more personalized and effective treatment for patients with specific genetic profiles. ^{1 2 4 5 6}

What is the purpose of this trial?

This is a study of select drug therapies in patients with salivary gland cancer. The study has two phases: a molecular profiling phase (phase 1) and a treatment phase (phase 2). Based on the Molecular profiling results in phase the participants will receive matched treatment if a specific aberration is identified or will receive treatment with Selinexor if unmatched and no druggable aberration is identified.

Research Team

Anna Spreafico, MD PhD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for adults with advanced salivary gland cancer that has returned or spread, and there's no cure available. Participants need to have a measurable tumor, good heart and organ function, and no serious heart issues or drugs affecting their heartbeat. They must show disease progression and provide tissue samples for gene testing.

Inclusion Criteria

My diagnosis of a salivary gland tumor was confirmed through testing.

My cancer is getting worse as shown by tests or how I feel.

(Phase 2, Treatment) If the matched treatment is in the context of another phase I trial, the eligibility criteria of the enrolled trial will be used instead of the criteria from this trial

Exclusion Criteria

My tumor does not have enough tissue for detailed genetic testing.

I stopped my last treatment without my cancer getting worse.

I have previously received the same drug that I will be assigned in phase 2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Profiling

Participants provide a sample of their tumor tissue to test for changes in certain genes

4 weeks

Treatment

Participants receive matched treatment based on molecular profiling results or Selinexor if unmatched

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Anti-androgen
• C-KIT Inhibitor
• EGFR or HER2 Inhibitor
• FGFR Inhibitor
• MEK or PI3K Inhibitor
• NOTCH Inhibitor
• Selinexor

Trial Overview The study tests various drug therapies tailored to genetic abnormalities in salivary gland cancers. If specific gene changes are found, patients get matched treatments; otherwise, they receive Selinexor. It includes initial gene profiling followed by treatment based on the results.

Participant Groups

Group I: Unmatched Treatment (Selinexor) Experimental Treatment 1 Intervention

Selinexor, 30mg/m2, by mouth, twice weekly, every 28 day cycles. If patients have a "druggable" aberration but there is no access to the relevant agent, then patients will receive selinexor

Group II: Matched Therapy Experimental Treatment 6 Interventions

EGFR or HER2 Inhibitor,FGFR Inhibitor,C-KIT Inhibitor, Anti-androgen ,NOTCH Inhibitor,MEK or PI3K Inhibitor . If the matched therapy is given through a clinical trial, the dosing schedule will be determined by that particular trial protocol. For matched treatments administered outside of a clinical trial, the dosing schedule will be the recommended dose by the expertise of the treating investigator.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study of 19 patients with recurrent or metastatic salivary gland carcinoma (SGC) treated with the EXTREME regimen, 77.8% showed overexpression of the epidermal growth factor receptor (EGFR), but this did not correlate with better clinical outcomes.

The treatment response was limited, with only two patients achieving a partial response and the regimen being discontinued for all patients, indicating that while SGCs often express EGFR, the EXTREME regimen may not be effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer. Nakano, T., Yasumatsu, R., Hashimoto, K., et al.[2022]

Salivary gland carcinomas (SGC) have historically been difficult to treat with standard chemotherapy and immunotherapy, but recent discoveries of targetable molecular alterations have led to improved treatment outcomes.

Identified alterations such as HER2 upregulation and NTRK gene fusions are paving the way for precision therapies, with ongoing clinical trials exploring these new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A molecular guide to systemic therapy in salivary gland carcinoma. Weaver, AN., Lakritz, S., Mandair, D., et al.[2023]

References

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

Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs). [2022]

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

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer. [2022]

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

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling. [2021]

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

Fluorescence in situ hybridization gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors treated with lapatinib. [2021]

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

Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy. [2021]

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

A molecular guide to systemic therapy in salivary gland carcinoma. [2023]