Targeted Therapy for Salivary Gland Cancer

AH
AS
Overseen ByAnna Spreafico
Age: 18+
Sex: Any
Trial Phase: Academic
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores drug therapies for individuals with salivary gland cancer. It consists of two phases: first, testing tumor samples for specific changes, and second, administering treatments based on those results. If a tumor has a particular target, a matched drug will be administered; if not, the patient will receive Selinexor, a targeted therapy. Individuals with advanced salivary gland cancer that has spread or recurred and whose disease has worsened might be suitable candidates for this trial.

As an unphased study, this trial provides a unique opportunity to access personalized treatments based on the specific characteristics of the tumor.

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.

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

Research shows that the safety of treatments in this trial depends on the specific drugs used. For treatments like EGFR or HER2 inhibitors, studies have examined their effects in cancer treatment. These treatments are usually well-tolerated, but side effects can include skin rash and diarrhea due to their targeted action on cancer cells.

For patients taking Selinexor, research indicates that this drug can cause side effects like nausea and fatigue, but it specifically targets cancer cells while sparing normal ones. In past studies on recurring or spreading salivary gland tumors, Selinexor demonstrated a manageable safety profile. However, patients should be aware of possible side effects like low blood cell counts. This drug has already received FDA approval for other uses, confirming its basic safety.

In summary, while each treatment may have side effects, studies suggest they are generally manageable. Participants should consult their doctors about potential risks to understand what to expect.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for salivary gland cancer because they offer a targeted approach that goes beyond traditional chemotherapy and radiation. While most current treatments focus on broadly attacking fast-growing cancer cells, these investigational drugs target specific pathways and mutations that are driving the cancer. For example, the EGFR or HER2 inhibitors specifically block growth signals in cancer cells with those markers, and selinexor works by interfering with the cancer cells' ability to regulate proteins and grow. This precision targeting could potentially lead to more effective treatments with fewer side effects.

What evidence suggests that this trial's treatments could be effective for salivary gland cancer?

Research has shown that certain treatments can be effective for salivary gland cancer. In this trial, participants may receive a matched therapy, which could include NOTCH inhibitors, HER2 inhibitors, or FGFR inhibitors, among others. NOTCH inhibitors have performed better than merely monitoring the cancer or using older treatments. HER2 inhibitors have also shown promise, even for patients who have tried other treatments before. FGFR inhibitors have demonstrated strong effects against tumors in lab studies.

For patients in this trial without specific genetic changes that can be targeted, selinexor serves as an unmatched treatment. Although it hasn't led to significant tumor shrinkage in studies, it has helped many patients prevent their cancer from growing further. Overall, these treatments offer potential ways to manage salivary gland cancer.23678

Who Is on the Research Team?

Anna Spreafico | UHN Research

Anna Spreafico, MD PhD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

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) Not receiving any other concurrent investigational agent
See 15 more

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.
See 2 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Unmatched Treatment (Selinexor)Experimental Treatment1 Intervention
Group II: Matched TherapyExperimental Treatment6 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+

Published Research Related to This Trial

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

Citations

Advances in Targeted and Systemic Therapy for Salivary ...This review discusses the current landscape of treatment options and explores promising clinical trials and future directions to enhance outcomes for patients ...
Clinical Outcomes With Notch Inhibitors in Notch‐Activated ...NOTCH inhibitors demonstrate activity in NOTCH‐activated ACC, surpassing the efficacy of observation or prior systemic therapies.
Review HER2-targeted therapies for salivary gland cancersA phase I trial showed that A166 had an acceptable toxicity profile and it was clinically effective in heavily pretreated patients with relapsed or refractory ...
Palliative systemic therapy for locally advanced or ...Although BRAF mutations are infrequent in salivary gland cancers, SDC exhibits a relatively high frequency, accounting for approximately 5 % of cases [58,61,62] ...
Targeting FGFR for cancer therapyInfigratinib is a potent and selective inhibitor of FGFR1, 2 and 3 that has demonstrated significant anti-tumor efficacy in preclinical studies ...
Systemic therapies for salivary gland adenoid cystic ...The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%.
Targeting the EGFR signaling pathway in cancer therapy - PMCIn this review, the basic mechanism of EGFR activation and the role of EGFR signaling in cancer progression, has been covered.
Molecular Targets in Salivary Gland CancersSGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy.
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