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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Sunitinib for cancer?

Sunitinib has been shown to be effective in treating advanced renal cell carcinoma (RCC) with a 37% response rate and 48% stable disease, and it is also used for gastrointestinal stromal tumors (GIST) with an 8% response rate and 70% stable disease. It has shown moderate activity in breast cancer and some effectiveness in non-small cell lung cancer (NSCLC) as well. ^{1 2 3 4 5}

What is known about the safety of Sunitinib in humans?

Sunitinib is generally safe for humans but can cause side effects like fatigue, diarrhea, skin rash, and high blood pressure. It may also lead to more serious issues like low blood cell counts and thyroid problems, so careful monitoring by a doctor is important. ^{3 4 6 7 8}

How is the drug Sunitinib unique in cancer treatment?

Sunitinib is unique because it is a multitargeted tyrosine kinase inhibitor that blocks several pathways crucial for tumor growth and blood vessel formation, making it effective in treating various cancers like renal cell carcinoma and gastrointestinal stromal tumors. It works by inhibiting receptors such as VEGF and PDGF, which are involved in angiogenesis (formation of new blood vessels) and tumor cell proliferation. ^{1 3 4 5 9}

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well sunitinib in treating patients with cancer that has certain genetic changes. Sunitinib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the cKIT gene. It works by blocking the action of mutated cKIT that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Research Team

Lilian T Gien

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Sunitinib inhibits MEK/ERK and SAPK/JNK pathways and increases sodium/iodide symporter expression in papillary thyroid cancer. [2018]

5. England 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. [2018]

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

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

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

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

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

Nonclinical safety evaluation of sunitinib: a potent inhibitor of VEGF, PDGF, KIT, FLT3, and RET receptors. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Early experience with sunitinib, combined with docetaxel, in patients with metastatic breast cancer. [2018]