Sunitinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Heart disease, Stroke, Pulmonary embolism, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 42 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well sunitinib treats cancer in people with certain genetic changes. Sunitinib blocks signals that prompt cancer cells to multiply, potentially stopping or slowing cancer spread. The study seeks patients with cancer who have specific changes in the cKIT gene. Those who have not recently experienced certain heart issues or surgeries and do not have specific cancers, such as gastrointestinal stromal tumors, may qualify for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important cancer research.

Will I have to stop taking my current medications?

The trial requires that you avoid taking strong CYP3A4 inhibitors or inducers before and during the study. If you are on these medications, you may need to stop them 7 to 12 days before starting the trial. Check with your doctor to see if your current medications fall into this category.

Is there any evidence suggesting that sunitinib is likely to be safe for humans?

Research has shown that sunitinib is generally safe for people. Studies have found it effective for patients with various cancers, including breast and kidney cancer. In breast cancer patients who had undergone many previous treatments, sunitinib reduced cancer size in 11% of cases. For kidney cancer, patients taking sunitinib lived longer, with some using the drug for over six years.

One study found that patients with advanced kidney cancer tolerated a 37.5 mg dose of sunitinib well, experiencing the drug's effects without major safety issues. This suggests that sunitinib is usually well-tolerated, even with long-term use. However, like any treatment, side effects can occur, so discussing potential risks with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sunitinib is unique because it targets specific proteins involved in cancer cell growth, offering a more focused approach compared to traditional chemotherapy. While most cancer treatments attack rapidly dividing cells indiscriminately, sunitinib works by inhibiting tyrosine kinases, which are enzymes that promote tumor blood vessel growth. This targeted action not only helps to starve the tumor of nutrients but also potentially reduces some of the harsh side effects associated with less specific cancer treatments. Researchers are excited about sunitinib because it offers a novel mechanism that may improve effectiveness and tolerability for patients.

What evidence suggests that sunitinib might be an effective treatment for cancer?

Research has shown that sunitinib, the treatment under study in this trial, can effectively treat certain cancers. For patients with advanced kidney cancer, one study associated sunitinib with a longer survival time of 31.7 months compared to another treatment. Another study found that sunitinib helped patients with high-risk kidney cancer remain disease-free for an average of 6.8 years. Additionally, in a different study, 15.7% of patients taking sunitinib experienced tumor shrinkage. These studies suggest that sunitinib can be effective for cancers with specific genetic changes, such as mutations in the cKIT gene. ^{2 6 7 8 9}

Who Is on the Research Team?

Lilian T Gien

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with a specific genetic change in the cKIT gene. It's open to those with lymphoma, multiple myeloma, or solid tumors who meet certain health standards. People are excluded if they don't have the cKIT mutation or if their health conditions make it unsafe to participate.

Inclusion Criteria

Total bilirubin must be within normal institutional limits

My kidney function is normal or meets the required levels for the study.

Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)

Exclusion Criteria

My thyroid condition cannot be controlled with medication.

I haven't had any major abdominal issues like a fistula, perforation, or abscess in the last 28 days.

I am allergic or had a bad reaction to sunitinib or similar drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sunitinib 50 mg orally once daily on days 1-28 of each 42-day cycle

42 days per cycle

Regular visits for CT/MRI, ECHO, and biopsies as clinically necessary

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Sunitinib

Trial Overview The trial is testing Sunitinib, a kinase inhibitor medication that targets cancers with cKIT mutations. Patients will undergo various assessments including biopsies and imaging tests like MRI and CT scans to see how well the treatment works.

How Is the Trial Designed?

Group I: Treatment (sunitinib) Experimental Treatment 7 Interventions

Patients receive sunitinib 50 mg PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 an oral medication that inhibits key pathways involved in tumor growth and blood vessel formation, making it a potential treatment for metastatic breast cancer.

In a report involving four patients with advanced breast cancer, combining sunitinib with docetaxel chemotherapy led to clinically meaningful responses, suggesting that this combination may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early experience with sunitinib, combined with docetaxel, in patients with metastatic breast cancer. Liljegren, A., Bergh, J., Castany, R.[2018]

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 effectively inhibits the growth and migration of papillary thyroid cancer cells with the RET/PTC1 rearrangement, demonstrating a dose-dependent effect with a mean lethal concentration of 1.81 microM.

The drug works by blocking specific signaling pathways (MEK/ERK and SAPK/JNK), leading to cell cycle arrest and increased expression of the sodium/iodide symporter (NIS), which is important for iodide metabolism in thyroid cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib inhibits MEK/ERK and SAPK/JNK pathways and increases sodium/iodide symporter expression in papillary thyroid cancer. Fenton, MS., Marion, KM., Salem, AK., et al.[2018]

Sunitinib (Sutent) is an effective treatment for metastatic renal cell carcinoma (RCC), showing a 37% response rate and 48% stable disease, making it the preferred first-line therapy for this cancer.

Sunitinib also demonstrates efficacy in gastrointestinal stromal tumors (GIST) with an 8% response rate and 70% stable disease, contributing to a median survival of 20 months, and shows moderate activity in breast cancer and non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors. Polyzos, A.[2018]

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 is generally well-tolerated in both Sprague-Dawley rats and cynomolgus monkeys at lower doses (0.3 mg/kg/day in rats and 1.5 mg/kg/day in monkeys), with most treatment-induced effects being reversible after cessation of treatment.

The study highlights that sunitinib's inhibition of multiple receptor tyrosine kinase pathways can lead to pharmacologic effects on organ systems, including reversible changes in neovascularization and reproductive organ development, which are consistent with the drug's mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety evaluation of sunitinib: a potent inhibitor of VEGF, PDGF, KIT, FLT3, and RET receptors. Patyna, S., Arrigoni, C., Terron, A., et al.[2019]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6684538/

Sunitinib for Metastatic Renal Cell Carcinoma Another independent study found that in Canadian patients, sunitinib was associated with an improved OS of 31.7 months compared with pazopanib ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1611406

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after ... The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1526820921001373

Clinical Breast Cancer Patients with ERpositive disease had the highest response rate (64%). Our data provide evidence that the addition of sunitinib to neoadjuvant chemotherapy may ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5943825/

Benefit, Risk, and Outcomes in Drug Development In total, 1052 patients in sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence ...

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2006.24.18_suppl.7001

Efficacy and safety of sunitinib in previously treated ... Stable disease has been observed in an additional 12 pts (19.0%). Survival data are pending and will be presented. Conclusions: Sunitinib has ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8611115/

A Phase II Study Evaluating the Safety and Efficacy ... Patients with ER positive disease had the highest response rate (64%). Our data provide evidence that the addition of sunitinib to neoadjuvant chemotherapy may ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00338884

Safety And Effectiveness Of Daily Dosing With 37.5 mg ... A phase II study to allow patients with advanced kidney cancer access to sunitinib malate treatment and to find out the good and bad effects of taking 37.5 mg ...

8. 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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5032140/

Long-term Safety of Sunitinib in Metastatic Renal Cell ... Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr.