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

NCT01108445 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro00020714CRAD001L2402T
• Study Type: interventional
• Target: 131
• Locations: 3 countries
• Sites: 18

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.

Conditions

Advanced Non-clear Cell Renal Cell Carcinoma

Keywords

cancer; kidney cancer; sutent; everolimus; renal cancer; papillary renal cell; chromophobe renal cell; papillary; chromophobe

Outcome Measures

Primary Outcomes (1)

• Anti-tumor Activity as Measured by Median Progression Free Survival Time

  The primary objective will be to compare the anti-tumor activity of everolimus and sunitinib in subjects with mRCC with non-clear cell pathology, as measured by progression-free survival (PFS) following treatment initiation according to RECIST 1.1 criteria. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  24 Months

Secondary Outcomes (14)

• Progression Free Survival Rates

  6, 12 and 24 months

• PFS Expressed in Months

  24 months

• Overall Response Rate

  24 months

• Percentage of Participants With Stable Disease (SD)

  Baseline to 36 months

• 12 Week Clinical Benefit Rate as Percentage

  Baseline to 36 months

Other Outcomes (2)

• Clinical Measures of Response and PFS With Baseline and Time-dependent Levels of Biomarkers

  36 months

• Changes in Copy Number, RNA Expression, and Immunohistochemical Profiles

  36 months

Study Arms (2)

RAD001

ACTIVE COMPARATOR

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.

Drug: Everolimus

Sunitinib

ACTIVE COMPARATOR

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

Drug: Sunitinib

Interventions

Everolimus 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.

Also known as: Afinitor, everolimus, RAD001

RAD001

Sunitinib DRUG

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

Also known as: Sutent

Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell pathology.
• RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both.
• 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.
• Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria (Attachment 1)\].
• Age \> 18 years.
• Adequate laboratory values
• Karnofsky Performance Status ≥ 60 (Attachment 2).
• Life expectancy of at least 3 months.
• 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.

You may not qualify if:

• Subjects with a history of or active central nervous system (CNS) metastases.
• Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy.
• Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology.
• Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
• Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit.
• Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
• Presence of a non-healing wound or ulcer.
• Grade 3 hemorrhage within the past month.
• Hypertension with systolic blood pressure of \>180 mm Hg and/or diastolic pressure \>100 mm Hg.
• 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.
• Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) \> 10% despite therapy.
• A history of interstitial pneumonitis.
• Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to the screening visit.
• Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV).
• Patients who have receive immunization with attenuated live vaccines within one week of study entry or during study period.

Sponsors & Collaborators

• Duke University: lead
• Novartis: collaborator
• Pfizer: collaborator

Study Sites (18)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University Melvin and Bran Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Karmanos Cancer Institute/Wayne State University

Detroit, Michigan, 48201, United States

Location

Washington Univ in St. Louis-School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke Univeristy Medical Center

Durham, North Carolina, 27708, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

SCRI

Nashville, Tennessee, 37203, United States

Location

The Vanderbilt Clinic, Henry-Joyce Cancer Center

Nashville, Tennessee, 37212, United States

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba, Med Onc, Dept Hem and Onc

Winnipeg, Manitoba, R3E 0V9, Canada

Location

London Health Sciences Center

London, Ontario, N6A-4L6, Canada

Location

Cambridge Cancer Trials Centre

Cambridge, England, CB2 0QQ, United Kingdom

Location

The Royal Marsden NHS

London, England, 8W3 6JJ, United Kingdom

Location

The Christie Hospital NHS

Manchester, England, M20 4BX, United Kingdom

Location

Weston Park Hospital

Sheffield, England, S10 2SJ, United Kingdom

Location

Churchill Hospital

Headington, Oxford, OX3 7LJ, United Kingdom

Location

Beatson West Scotland Cancer Centre

Glasgow, Scottland, G12 0YN, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37146227 DERIVED

• 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.

  PMID: 26794930 DERIVED

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

  PMID: 23228299 DERIVED

MeSH Terms

Conditions

Neoplasms; Kidney Neoplasms

Interventions

Everolimus; Sunitinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Andrew J Armstrong
• Organization: Duke University Medical Center

andrew.armstrong@duke.edu

919-668-4615

Study Officials

• Andrew Armstrong, MD, ScM

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2010
• First Posted: April 22, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2015
• Last Updated: January 16, 2018
• Results First Posted: June 20, 2016

Record last verified: 2017-09

Locations

GB (6); US (9); CA (3)