Savolitinib vs. Sunitinib for Kidney Cancer

Recruiting at 48 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 23-47 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed for patients diagnosed with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC, how it compares with another medication frequently used to treat this disease called sunitinib, and what side effects it might cause.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, including strong inducers or inhibitors of CYP3A4 and strong inhibitors of CYP1A2, at least 2 weeks before randomization. Herbal medications must be stopped 7 days before, and St John's wort 3 weeks before. If you are on any of these, you will need to stop them before participating.

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

Sunitinib has been shown to be effective for treating advanced kidney cancer, as it is a standard first-line treatment for patients with this condition. It works by targeting specific proteins in cancer cells, helping to slow down or stop their growth. ^{1 2 3 4 5}

What is the safety profile of Sunitinib for kidney cancer?

Sunitinib is generally safe for treating kidney cancer, but it can cause side effects like tiredness, diarrhea, skin rash, mouth sores, and changes in thyroid function. It may also lead to high blood pressure and changes in blood cell counts. ^{1 5 6 7 8}

How does the drug Savolitinib differ from Sunitinib for kidney cancer?

Sunitinib is a well-established drug for kidney cancer that works by blocking multiple proteins involved in tumor growth and blood vessel formation, making it effective in slowing disease progression. Savolitinib, on the other hand, is being compared to Sunitinib in trials, and its unique mechanism or benefits over Sunitinib are not detailed in the provided research. ^{3 8 9 10 11}

Research Team

Toni K Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with MET-driven, advanced Papillary Renal Cell Carcinoma (PRCC) that can't be surgically removed. It's open to those who haven't had treatment or have had previous systemic therapy. Participants need good blood, kidney, heart, and liver function and a high level of physical ability. They must not have other active cancers or recent cancer treatments, untreated brain metastases, or conditions affecting the heart's rhythm.

Inclusion Criteria

I have or haven't had systemic therapy for advanced PRCC.

My blood, kidney, heart, and liver functions are all within normal ranges.

I can carry out normal activities with minimal symptoms.

Exclusion Criteria

I haven't had major surgery in the last 4 weeks or minor surgery in the last week.

My brain cancer has not been treated yet.

I have not had treatment for any invasive cancer in the last 5 years, nor do I have any other active cancers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either savolitinib or sunitinib to assess efficacy and safety in treating MET-driven PRCC

23-47 weeks

RECIST tumour assessments every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Savolitinib
• Sunitinib

Trial Overview The study compares Savolitinib (a new anti-cancer medication) with Sunitinib (an established treatment), in patients with PRCC to see which is more effective and what side effects they might cause. Patients will be randomly assigned to receive either drug and monitored for results.

Participant Groups

Group I: Savolitinib Experimental Treatment 1 Intervention

See: intervention description

Group II: Sunitinib Active Control 1 Intervention

See: intervention description

Savolitinib is already approved in China for the following indications:

Approved in China as Orpathys for:

• Non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Hutchison Medipharma Limited

Industry Sponsor

Trials

104

Recruited

14,000+

Dr. Weiguo Su

Hutchison Medipharma Limited

Chief Executive Officer since 2022

PhD in Chemistry from Harvard University, BSc in Chemistry from Fudan University

Dr. Karen Atkin

Hutchison Medipharma Limited

Chief Medical Officer since 2023

MD from Harvard Medical School

Hutchinson MediPharma (HMP)

Collaborator

Trials

1

Recruited

60+

Findings from Research

In a study of 41 patients with advanced renal cell carcinoma and renal impairment, both sunitinib and sorafenib showed similar efficacy in terms of progression-free survival (6.6 months for sunitinib vs 5.8 months for sorafenib) and overall survival (65.9 months vs 58.0 months).

However, sunitinib was associated with a higher frequency of grade 3 or higher adverse events compared to sorafenib, indicating a need for careful monitoring of side effects, especially in patients with prior kidney surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. Takayama, T., Kubo, T., Yamazaki, M., et al.[2020]

Sunitinib is an effective treatment for advanced metastatic renal cell carcinoma (mRCC), showing a significant improvement in progression-free survival compared to interferon-alpha, with 11 months for sunitinib versus 5 months for interferon-alpha in a Phase III study.

In Phase II trials, sunitinib demonstrated a partial response rate of 40% and 34% as a second-line therapy for mRCC patients who did not respond to previous cytokine treatments, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. Chouhan, JD., Zamarripa, DE., Lai, PH., et al.[2018]

In a study of 49 patients with advanced renal cell carcinoma, those who received sorafenib followed by sunitinib (Group A) experienced a longer median duration of stable disease (20 weeks) compared to those who received sunitinib followed by sorafenib (Group B) with only 9.5 weeks.

Patients in Group A also had a longer median time to disease progression (78 weeks) compared to Group B (37 weeks), suggesting that the sequence of treatment may impact the effectiveness of these tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Dudek, AZ., Zolnierek, J., Dham, A., et al.[2022]

Sunitinib has been established as the standard first-line treatment for advanced renal cell carcinoma, based on results from a large-scale, long-term Phase III trial.

Conventional treatments like nephrectomy followed by IL-2 or IFN-alpha often do not provide long-term survival benefits, highlighting the importance of targeted therapies like sunitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. Hutson, TE.[2018]

In a study of 90 patients with renal cell carcinoma, sequential treatment with sorafenib followed by sunitinib resulted in a median overall survival of 135 weeks, compared to 82 weeks for the reverse sequence, indicating that the order of administration may impact survival outcomes.

Both treatment sequences were well tolerated, with no increase in severe toxicity (grade 3-4), suggesting that sequential administration of these tyrosine kinase inhibitors is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential sorafenib and sunitinib for renal cell carcinoma. Sablin, MP., Negrier, S., Ravaud, A., et al.[2018]

Sunitinib has a similar safety profile in patients undergoing nephrectomy for kidney cancer, whether used in the adjuvant setting or for metastatic disease, based on data from phase III trials including CARMENA and SURTIME.

Effective management of sunitinib's adverse effects is crucial, particularly in the adjuvant setting, where maintaining dose intensity and exposure can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. Heraudet, L., Domblides, C., Daste, A., et al.[2022]

Sunitinib, an oral tyrosine kinase inhibitor, has shown significant antitumor activity and improved progression-free survival in patients with renal cell carcinoma, based on phase II and III clinical trials.

Understanding the unique side effects of sunitinib is crucial for effective patient education, enabling better anticipation and management of these therapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. Schwandt, A., Wood, LS., Rini, B., et al.[2022]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. [2020]

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

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. [2018]

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

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. [2018]

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

Sequential sorafenib and sunitinib for renal cell carcinoma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma. [2022]

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

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

9. Spain pubmed.ncbi.nlm.nih.gov

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

10. Australia pubmed.ncbi.nlm.nih.gov

Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib. [2018]

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

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