Pilot Study of Neo-Adjuvant Everolimus to Treat Advanced Renal Cell Carcinoma - Analysis of Biomarkers

NCT01107509 | Completed

• 1 other identifier: MIURCCEVERO
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will gather data on potential biomarkers in the treatment of advanced renal cell carcinoma (kidney cancer) and investigate their use as indicators of disease response. The results could eventually enable doctors to match levels of therapy to levels of biomarker on an individual basis and to increase the chance of disease response in patients. This study will also test a new paradigm in the treatment approach of advanced kidney cancer by using the drug everolimus in a neo-adjuvant setting, with the overarching goal of decreasing cancer recurrence rates and improving patient outcomes and survival.

Conditions

Carcinoma, Renal Cell

Keywords

Renal cell carcinoma; Metastatic; everolimus; neo-adjuvant; biomarkers; nephrectomy; Locally advanced clear cell renal carcinoma; Metastatic clear cell renal carcinoma; Clear Cell Renal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Response of primary tumor and metastases (if applicable) to everolimus in terms of tumor size and appearance (RECIST imaging response criteria) as determined by CT or MRI

  From 6 weeks after starting neo-adjuvant everolimus until 1 year post-nephrectomy (or up to 24 months post-nephrectomy in metastatic patients)

Secondary Outcomes (1)

• Effect of everolimus on blood and tissue biomarker expression (periodic blood testing and tissue samples from baseline renal biopsy and nephrectomy) in and among patients with locally advanced and metastatic disease with respect to baseline values

  From baseline to 1 year post-nephrectomy for blood biomarker levels and from baseline to nephrectomy (week 12) for tissue biomarker levels

Study Arms (1)

Neo-adjuvant everolimus

EXPERIMENTAL

Drug: everolimus

Interventions

everolimus DRUG

10 mg/ day everolimus in the form of an oral tablet for 12 weeks leading up to nephrectomy (with a 1-week perioperative washout period) in patients with locally advanced disease and re-initiating the drug postoperatively in patients with metastatic disease for up to 24 months, or until disease progression. Dosage may be reduced at any point to 5 mg/ day in the event of any grade 3/ 4 toxicity.

Also known as: Afinitor, RAD-001

Neo-adjuvant everolimus

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age and capable of giving informed consent
• Radiological evidence of RCC consisting of: CT scan with stage T2, T3, T3a, T3b, T4, or any stage T with N1/ 2 and/ or metastatic disease
• Having a nephrectomy and willing to have a kidney biopsy
• ECOG score 0 or 1
• Clear cell histology
• Negative for HIV, Hepatitis B, and Hepatitis C
• Negative pregnancy test for women of child-bearing potential

You may not qualify if:

• Stage T1 disease without metastases
• Abnormal laboratory values at screening within the following ranges:
• Absolute neutrophil count ≤ 1.5 × 109/ L; Platelet count ≤ 100 × 109/ L
• Leukocyte count ≤ 3 × 109/ L; Hemoglobin ≤ 80 g/ L; Serum creatinine ≥ 2.0 × the upper normal limit (UNL); Total bilirubin ≤ 1.5 × UNL; AST and ALT ≤ 3.0 × UNL
• Fasting serum cholesterol ≤ 9.0 mmol/ L; Fasting serum triglycerides ≥ 5.0 mmol/L
• Any major illness that, based on the investigator's judgment, will substantially increase the risk associated with a subject's participation in this study
• Other currently active malignancies
• Currently taking any medications known to interfere with the metabolism of everolimus
• Receiving anticoagulation with warfarin
• A history of pulmonary hypertension or interstitial lung disease

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• McMaster University: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; 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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Anil Kapoor, MD, FRCSC

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FRCSC

Study Record Dates

• First Submitted: April 20, 2010
• First Posted: April 21, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: April 4, 2018

Record last verified: 2018-04

Locations

CA (1)