Immunotherapy for Advanced Rare Cancers

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

137 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done because there is no treatment that will cure this type of cancer. Although some types of chemotherapy can cause this cancer to shrink for a time, better options are needed.

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.

What data supports the effectiveness of the drug Sunitinib in combination with Temsirolimus for treating advanced rare cancers?

Sunitinib and Temsirolimus have been shown to be effective in treating metastatic renal cell carcinoma (a type of kidney cancer that has spread) by targeting different cancer growth pathways. Sunitinib has also demonstrated activity in other cancer types and can enhance immune responses, making it potentially beneficial when combined with immunotherapies. ^{1 2 3 4 5}

What safety data exists for Sunitinib and Temsirolimus in humans?

Sunitinib, used for certain kidney and stomach cancers, can cause side effects like fatigue, diarrhea, skin rash, and high blood pressure. Temsirolimus, used for advanced cancers, has been studied for its safety, but specific side effects are not detailed in the provided research. ^{6 7 8 9 10}

How is the drug Sunitinib unique for treating advanced rare cancers?

Sunitinib is unique because it is a multitargeted drug that blocks several pathways important for tumor growth, specifically targeting receptors involved in blood vessel formation, which is crucial for treating rare cancers with high blood vessel density. ^{11 12 13 14 15}

Research Team

Hal Hirte

Principal Investigator

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

Eligibility Criteria

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.

You are pregnant or breastfeeding.

You are allergic to the study drug or any of its ingredients.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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 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 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]

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]

References

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

Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Sunitinib in the treatment of metastatic renal cell carcinoma. [2020]

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

A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma. [2023]

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

Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma. [2022]

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

Consequence of dose scheduling of sunitinib on host immune response elements and vaccine combination therapy. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibition in renal cell carcinoma and gastrointestinal stromal tumours: case reports. [2020]

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

The use of sunitinib in renal cell carcinoma: where are we now? [2018]

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

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. [2022]

10. United States 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. [2014]

11. England pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports. [2022]

13. Spain pubmed.ncbi.nlm.nih.gov

Sunitinib: a newly approved small-molecule inhibitor of angiogenesis. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer. [2021]

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

A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. [2022]