Everolimus for Kidney Cancer

(S0931 Trial)

No longer recruiting at 1022 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, Systemic steroids, Immunosuppressants

Disqualifiers: Cardiac disease, Liver disease, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of everolimus in treating kidney cancer after surgery. Everolimus aims to stop tumor growth by blocking certain enzymes or cutting off the tumor's blood supply. The trial includes two groups: one takes everolimus, and the other takes a placebo (a pill with no active drug). Suitable participants have undergone kidney cancer surgery, with no cancer spread to other parts of the body and no remaining cancer visible on recent scans. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inhibitors or inducers, live vaccines, or chronic systemic steroids. Topical or inhaled corticosteroids are allowed.

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

Research has shown that everolimus is generally well-tolerated by people with kidney cancer. In studies involving patients with advanced kidney cancer, everolimus provided a good balance between benefits and side effects. One study found that patients taking everolimus lived longer than those who did not, with an average survival time of 14.8 months.

While everolimus is effective, some patients experienced side effects. Common ones included mouth sores and fatigue. Importantly, most people found these side effects manageable. Everolimus has also been used safely in patients with other types of cancer, supporting its safety. Overall, everolimus appears to be a reliable option for treating kidney cancer after surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney cancer?

Unlike the standard treatments for kidney cancer, which often include surgery, targeted therapies, and immunotherapy, everolimus works differently by inhibiting a protein called mTOR, which plays a key role in cancer cell growth and survival. Researchers are excited about everolimus because it targets this specific pathway, potentially slowing tumor growth more effectively. Additionally, everolimus is administered orally, making it a convenient option compared to some treatments that require intravenous administration. This unique mode of action and delivery offers hope for improved outcomes in managing kidney cancer.

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

Research has shown that everolimus, which participants in this trial may receive, effectively treats metastatic renal cell carcinoma (mRCC). Studies have found that everolimus can extend the period patients live without their cancer worsening, known as progression-free survival (PFS). In some cases, it increased PFS from 4 months to about 8 months. Everolimus stops tumor growth by cutting off the blood supply tumors need, making it a promising option for treating kidney cancer when other treatments have failed. ^{1 5 6 7 8}

Who Is on the Research Team?

Christopher W. Ryan, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults who've had surgery for kidney cancer, with no remaining or spreading cancer detectable by CT/MRI scans. They should be in good physical condition (Zubrod status 0-1), have proper organ function, and not be pregnant. Participants must use effective contraception and be able to take oral medications. Those with heart disease, severe liver impairment, HIV, uncontrolled diabetes or cholesterol levels, allergies to everolimus components, or other recent cancers are excluded.

Inclusion Criteria

My kidney cancer has spread to small blood vessels but not to distant parts.

My condition is classified as intermediate high-risk or very high-risk.

I have had surgery to remove my kidney and any affected lymph nodes.

Exclusion Criteria

I have unstable chest pain.

I have severe heart disease.

I have not had a heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral everolimus or placebo once daily for 54 weeks, with treatment repeating every 6 weeks for 9 courses

54 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years every 6 months, then annually for 8 years

Every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus

Trial Overview The study is testing the effectiveness of Everolimus in preventing kidney cancer from returning after surgery. Patients will either receive Everolimus or a placebo (a pill without active medication) to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: Arm I Experimental Treatment 1 Intervention

Patients receive oral everolimus once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm II Placebo Group 1 Intervention

Patients receive oral placebo once daily on days 1-42. Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

Everolimus is already approved in United States, European Union for the following indications:

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Everolimus, used in combination with aromatase inhibitors for treating metastatic ER-positive and HER2-negative breast cancer, can lead to serious side effects like interstitial lung disease and acute kidney injury.

This case highlights a patient who developed Pneumocystis pneumonia without typical respiratory symptoms and acute kidney injury while on everolimus, emphasizing the need for careful monitoring of lung and kidney health during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumocystis Pneumonia and Acute Kidney Injury Induced by Everolimus Treatment in a Patient with Metastatic Breast Cancer. Nakamura, M., Matsunuma, R., Yamaguchi, K., et al.[2020]

Everolimus, an oral mTOR inhibitor, significantly improves progression-free survival in patients with clear cell renal cancer, increasing it from a median of 1.9 months to 4.9 months in a phase III trial with a hazard ratio of 0.33 (P < 0.001).

The treatment is generally well-tolerated, with mild to moderate side effects that can be managed, and it has been approved as a validated option for patients who have progressed on VEGFR inhibitors, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. Coppin, C.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20549832/

Phase 3 trial of everolimus for metastatic renal cell carcinoma Conclusions: These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib. © 2010 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4549702/

Clinical experience with everolimus in the second-line ... The median treatment duration was 6.5 months and in patients who received everolimus as second-line treatment the median time to progression and PFS were 7.1 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1510016

Cabozantinib versus Everolimus in Advanced Renal-Cell ... Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291813010230

Cost-Effectiveness of Everolimus for Second-Line ... New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months.

5. apm.amegroups.org apm.amegroups.org/article/view/60644/html

Clinical analysis of everolimus in the treatment of metastatic ... Results: Everolimus extended progression-free survival (PFS) in mRCC patients from 4 to 8 months (median 6.3 months). There were 3 patients with PR, 12 with SD, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0959804919308123

Outcomes based on age in the phase III METEOR trial of ... PFS, OS and ORR were improved with cabozantinib compared with everolimus in all age subgroups. The PFS hazard ratios (HRs) were 0.53 (95% confidence ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1510665

Nivolumab versus Everolimus in Advanced Renal-Cell ... Among patients with less than 1% PD-L1 expression, the median overall survival was 27.4 months (95% CI, 21.4 to not estimable) in the nivolumab ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.25219

Phase 3 trial of everolimus for metastatic renal cell carcinoma Mature survival results show that the median OS was 14.8 months for patients treated with everolimus. A beneficial effect on survival for ...