Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma

NCT ID: NCT01108445

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2015-04-30

Brief Summary

To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic renal cell carcinoma (mRCC) with non-clear cell pathology.

Detailed Description

This will be an international (USA, Canada, and UK) open-label, outpatient, multicenter, randomized study of treatment with RAD001 (everolimus (Afinitor®) or sunitinib (Sutent®) in subjects with mRCC and non-clear cell histology. Special emphasis is placed on papillary and chromophobe histologies while sarcomatoid clear cell variants, medullary, and collecting duct carcinomas will be excluded (see eligibility). Subjects may continue receiving study drugs until disease progression, unacceptable toxicities, or withdrawal of consent, for a maximum of 24 months. Continuation of study assigned treatment will be allowed beyond 24 months at the discretion of the sponsor. Stratification variables will include histology (papillary vs. chromophobe) and Motzer risk criteria (0, 1-2, and 3). Tumor progression will be assessed locally and by independent review, in strict accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria measured every 12 weeks. At the time of progression, subjects will be taken off study other than simple administrative mortality follow-up. Primary pathologic samples and plasma/urine angiokine levels at baseline and over time will be collected and stored centrally for biomarker analysis.

Conditions

Advanced Non-clear Cell Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAD001

Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

Group Type: ACTIVE_COMPARATOR

Everolimus

Intervention Type: DRUG

Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

Sunitinib

Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Group Type: ACTIVE_COMPARATOR

Sunitinib

Intervention Type: DRUG

50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Interventions

Everolimus

Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.

Intervention Type: DRUG

Sunitinib

50 mg daily by mouth on days 1 through 28 of each 42 day cycle.

Intervention Type: DRUG

Other Intervention Names

Afinitor, everolimus, RAD001; Sutent

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell pathology.

2. RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both.

3. At the time of screening, at least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 4.0) Grade 1.

4. Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria (Attachment 1)].

5. Age > 18 years.

6. Adequate laboratory values

7. Karnofsky Performance Status ≥ 60 (Attachment 2).

8. Life expectancy of at least 3 months.

9. Written, signed, dated, and witnessed Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) approved informed consent form (ICF) before any screening procedures are performed.

Exclusion Criteria

1. Subjects with a history of or active central nervous system (CNS) metastases.

2. Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy.

3. Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology.

4. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.

5. Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit.

6. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.

7. Presence of a non-healing wound or ulcer.

8. Grade 3 hemorrhage within the past month.

9. Hypertension with systolic blood pressure of >180 mm Hg and/or diastolic pressure >100 mm Hg.

10. Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <50%, or history of unstable angina, myocardial infarction, coronary artery bypass graft, cerebrovascular accident, transient ischemic attack, or pulmonary embolism within 6 months of entry.

11. Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) > 10% despite therapy.

12. A history of interstitial pneumonitis.

13. Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to the screening visit.

14. Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV).

15. Patients who have receive immunization with attenuated live vaccines within one week of study entry or during study period.

16. Patients with active infection(s), active antimicrobial therapy or serious intercurrent illness.

17. History of other prior malignancy in past 5 years.

18. Pregnant or nursing women.

19. Major medical/psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications and history of noncompliance to medical regimens.

20. Known hypersensitivity to any of the components in everolimus or sunitinib product

21. Subjects taking agents that significantly prolong the QTc interval are not eligible.

22. Proteinuria with a spot urine protein/creatinine ratio >2 or 24 hour urine protein >2 grams per 24 hours.

23. Severely impaired lung function as defined as spirometry and Carbon Monoxide Diffusing Capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.

24. Advanced liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Armstrong, MD, ScM

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

University of Chicago

Chicago, Illinois, United States

Indiana University Melvin and Bran Simon Cancer Center

Indianapolis, Indiana, United States

Karmanos Cancer Institute/Wayne State University

Detroit, Michigan, United States

Washington Univ in St. Louis-School of Medicine

St Louis, Missouri, United States

Duke Univeristy Medical Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

SCRI

Nashville, Tennessee, United States

The Vanderbilt Clinic, Henry-Joyce Cancer Center

Nashville, Tennessee, United States

BC Cancer Agency

Vancouver, British Columbia, Canada

CancerCare Manitoba, Med Onc, Dept Hem and Onc

Winnipeg, Manitoba, Canada

London Health Sciences Center

London, Ontario, Canada

Cambridge Cancer Trials Centre

Cambridge, England, United Kingdom

The Royal Marsden NHS

London, England, United Kingdom

The Christie Hospital NHS

Manchester, England, United Kingdom

Weston Park Hospital

Sheffield, England, United Kingdom

Churchill Hospital

Headington, Oxford, United Kingdom

Beatson West Scotland Cancer Centre

Glasgow, Scottland, United Kingdom

Countries

United States; Canada; United Kingdom

References

Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

Reference Type: DERIVED

PMID: 37146227 (View on PubMed)

Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-388. doi: 10.1016/S1470-2045(15)00515-X. Epub 2016 Jan 13.

Reference Type: DERIVED

PMID: 26794930 (View on PubMed)

Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.

Reference Type: DERIVED

PMID: 23228299 (View on PubMed)

Other Identifiers

CRAD001L2402T

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00020714

Identifier Type: -

Identifier Source: org_study_id