Immunotherapy for Advanced Rare Cancers

Not currently recruiting at 16 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Anticoagulants, CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Other malignancies, Brain metastases, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Varies

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medicines, sunitinib (a type of targeted therapy) and temsirolimus (an mTOR inhibitor), to determine if they can more effectively treat certain rare, advanced cancers that currently lack a cure. Researchers aim to find more effective treatments since current options like chemotherapy provide only short-term benefits. Eligible participants have specific rare cancers, such as certain thyroid or liver cancers, that cannot be surgically removed or have metastasized. Participants should have tried other treatments but not medicines similar to sunitinib or temsirolimus. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications known as potent inhibitors or inducers of cytochrome P450 (CYP3A4) before starting the study. You must be off these medications 7-12 days prior to the first dose of sunitinib. Please consult with your doctor to review your current medications.

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

Previous studies have used Sunitinib to treat various cancers, such as advanced kidney cancer and a rare stomach cancer called GIST. Although some patients experienced serious side effects, including liver problems, these occurred in less than 1% of cases. This indicates that Sunitinib is generally well-tolerated but carries some risks.

Research has shown that Temsirolimus can help with advanced kidney cancer and is more effective than interferon alfa. While side effects can occur, studies did not find any common severe issues, suggesting that Temsirolimus is also fairly safe, though individual reactions may vary.

Both treatments have approval for use in other cancers, indicating a level of safety for humans. Nonetheless, joining any trial requires considering these factors, so staying informed is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sunitinib and Temsirolimus for treating advanced rare cancers because they offer new ways to target cancer cells. Unlike conventional treatments like chemotherapy, which indiscriminately attack rapidly dividing cells, Sunitinib works by inhibiting specific proteins involved in tumor growth and blood vessel development, making it a more targeted therapy. Temsirolimus, on the other hand, is unique as it blocks a protein called mTOR, which plays a crucial role in cancer cell growth and survival. These mechanisms of action give researchers hope for more effective and potentially less toxic treatment options for patients battling rare cancers.

What evidence suggests that this trial's treatments could be effective for advanced rare cancers?

Research has shown that sunitinib, one of the treatments in this trial, effectively treats certain advanced cancers. Specifically, it has extended the time patients with pancreatic tumors live without their cancer worsening, increasing this period from 5.5 to 11.1 months. Sunitinib also proves effective for advanced kidney cancer, offering better results than some other treatments.

Temsirolimus, another treatment option in this trial, has demonstrated effectiveness for advanced kidney cancer. It has helped patients live longer overall and delay cancer progression compared to other treatments. Temsirolimus is considered a strong option for patients with advanced cancers. Both treatments have shown promise in making some cancers more manageable. ^{1 6 7 8 9}

Who Is on the Research Team?

Hal Hirte

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Are You a Good Fit for This Trial?

This trial is for patients with advanced rare tumors who have measurable disease, are over 16 years old (or over 5 for a specific cohort), and have an ECOG performance status of 0-2. They should not have received certain prior treatments and must meet lab requirements. Exclusions include cardiovascular issues, recent heart or brain events, inability to absorb oral meds, known drug sensitivities, other cancer histories or concurrent cancer treatments.

Inclusion Criteria

I am at least 16 years old, or at least 5 for a specific study group.

Laboratory requirements met (hematology, chemistry)

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I have had cancer before, but it was a specific type that is allowed.

I have brain metastases that are causing symptoms.

You are pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sunitinib initially, and if ineffective, temsirolimus is administered

Varies

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Translational Research

Genetic analysis and other evaluations are conducted using primary tumour tissue specimens and baseline blood samples

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Sunitinib
• Temsirolimus

Trial Overview The study tests Sunitinib and Temsirolimus in patients with no cure-available cancers to see if these drugs can shrink the tumors. It's a Phase II trial which means it's checking the effectiveness of these drugs on this particular type of tumor after initial safety has been established.

How Is the Trial Designed?

Group I: Sunitinib Active Control 1 Intervention

Group II: Temsirolimus Active Control 1 Intervention

Sunitinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

Approved in European Union as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor
• Pancreatic Neuroendocrine Tumors

Approved in Canada as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

Approved in Japan as Sutent for:

• Renal Cell Carcinoma
• Gastrointestinal Stromal Tumor

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a phase II study involving 47 patients with advanced non-small cell lung cancer (NSCLC), sunitinib showed a low objective response rate of 2.1%, but 23.4% of patients experienced stable disease for at least 8 weeks, indicating some potential for disease control.

The treatment was generally well tolerated, with a median progression-free survival of 11.9 weeks and a median overall survival of 37.1 weeks, suggesting that sunitinib may be a viable option for patients who have not responded to platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. Novello, S., Scagliotti, GV., Rosell, R., et al.[2021]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

Sunitinib malate has shown long-term efficacy and safety in treating metastatic renal cell carcinoma (mRCC) and advanced imatinib-refractory gastrointestinal stromal tumors (GIST), as demonstrated in four patient cases.

Effective management of adverse events (AEs) allowed patients to continue long-term therapy with sunitinib, leading to sustained clinical benefits and prolonged responses in both mRCC and GIST cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibition in renal cell carcinoma and gastrointestinal stromal tumours: case reports. Schöffski, P., Bukowski, R., Flodgren, P., et al.[2020]

Sunitinib malate is a small molecule kinase inhibitor effective against various tyrosine kinase receptors and has recently been approved for treating advanced pancreatic neuroendocrine tumors, in addition to its existing approvals for renal cell carcinoma and gastrointestinal stromal tumors.

The use of sunitinib in treating rare tumors like peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL), and epithelioid hemangioendothelioma (EHE) is promising due to these tumors' overexpression of pro-angiogenic factors, suggesting that sunitinib may help manage these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports. Prochilo, T., Savelli, G., Bertocchi, P., et al.[2022]

Sunitinib is an effective treatment for metastatic renal cell carcinoma (mRCC) in Japan, showing high therapeutic response and prolonged survival, but it has a distinct toxicity profile that requires careful monitoring.

The most common severe side effect of sunitinib is myelotoxicity, particularly thrombocytopenia, affecting 73% of patients, with 36.8% experiencing grade 3 or higher toxicity, indicating the need for dose adjustments and individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. Kanda, H., Masui, S., Yamada, Y., et al.[2018]

Sunitinib malate (Sutent) was approved by the FDA for treating gastrointestinal stromal tumors (GIST) after patients showed disease progression or intolerance to imatinib, demonstrating a median time-to-tumor progression of 27.3 weeks compared to 6.4 weeks for placebo.

In advanced renal cell carcinoma, sunitinib showed partial response rates of 25.5% and 36.5% in two studies, with median response durations of 27.1 and 54 weeks, although it was associated with common side effects like diarrhea and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Goodman, VL., Rock, EP., Dagher, R., et al.[2022]

In a study involving 63 patients with advanced cancer, temsirolimus was found to be generally well tolerated, with a maximum tolerated dose established at 15 mg/m²/day for heavily pretreated patients and 19 mg/m²/day for minimally pretreated patients.

The treatment showed promising preliminary antitumor activity, with one patient achieving a confirmed partial response lasting 12.7 months, and several others showing stable disease for over 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Hidalgo, M., Buckner, JC., Erlichman, C., et al.[2014]

Sunitinib is an effective first-line treatment for metastatic renal cell cancer (mRCC), showing superiority over interferon alpha in a phase III trial, but it comes with significant side effects like diarrhea, hypertension, and fatigue.

An alternative dosing schedule of sunitinib (2 weeks on, 1 week off) may offer similar efficacy with better tolerability, and ongoing trials are exploring its use alongside newer immune checkpoint inhibitors in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in the treatment of metastatic renal cell carcinoma. Schmid, TA., Gore, ME.[2020]

In a Phase III trial involving treatment-naive patients with metastatic renal cell carcinoma (mRCC), sunitinib significantly improved progression-free survival compared to IFN-α, demonstrating its efficacy as a first-line treatment.

Sunitinib is effective even in challenging cases, such as patients with non-clear cell histology or those who are refractory to other treatments, and while it has common side effects like fatigue and hypertension, these may also indicate better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of sunitinib in renal cell carcinoma: where are we now? Czarnecka, AM., Szczylik, C., Rini, B.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5313263/

Sunitinib: Ten Years of Successful Clinical Use and Study in ... The patient‐reported outcomes were largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. A randomized ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1003825

Sunitinib Malate for the Treatment of Pancreatic ... Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as ...

3. sutent.com sutent.com/advanced-RCC

Advanced Kidney Cancer | SUTENT® (sunitinib malate) SUTENT has been proven effective in the treatment of advanced renal cell carcinoma (RCC). A clinical trial proved that SUTENT is more effective than IFNα.

4. pfizer.com pfizer.com/news/press-release/press-release-detail/sutent_significantly_improved_progression_free_survival_for_patients_with_advanced_pancreatic_islet_cell_tumors

Sutent Significantly Improved Progression-Free Survival for ... Results showed that median PFS was 11.1 months in patients treated with sunitinib compared to 5.5 months in patients treated in the placebo arm ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/13/5/1367/195746/Approval-Summary-Sunitinib-for-the-Treatment-of

Approval Summary: Sunitinib for the Treatment of Imatinib ... Median time-to-tumor progression of sunitinib-treated patients was 27.3 weeks, compared with 6.4 weeks for placebo-treated patients (P < 0.0001).

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/021938s027lbl.pdf

SUTENT (sunitinib malate) Label - accessdata.fda.gov SUTENT is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or ...

7. sutent.com sutent.com/GIST

GIST | SUTENT® (sunitinib malate) | Safety Info SUTENT is used to treat GIST (gastrointestinal stromal tumor). This is a rare cancer of the stomach, bowel, or esophagus.

8. mayoclinic.org mayoclinic.org/drugs-supplements/sunitinib-oral-route/description/drg-20070841

Sunitinib (oral route) - Side effects & dosage Sunitinib is also used to treat advanced (late-stage) kidney cancer ... Safety and efficacy have not been established. Geriatric.

9. labeling.pfizer.com labeling.pfizer.com/showlabeling.aspx?id=607

prescribing information for SUTENT SUTENT can cause severe hepatotoxicity, resulting in liver failure or death. In the pooled safety population, liver failure occurred in <1% of patients in ...