Everolimus/Sorafenib or Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC)

NCT01616186 | Withdrawn Phase 2 DMC

• 1 other identifier: UCSF CC# 12521
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II trial that follows the completion of the phase I UCSF trial of everolimus and sorafenib for Renal Cell Carcinoma (RCC). This trial will be for patients who have not had treatment for RCC before. This trial will have 2/3 patients getting everolimus/sorafenib treatment and 1/3 getting sunitinib, an FDA approved RCC drug. All three drugs are approved for advanced RCC when used individually, the combination of everolimus and sorafenib for RCC is not approved by the FDA.

Conditions

Locally Metastatic Malignant Neoplasm

Keywords

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response

  Computerized Tomography Scans (CT) done at Screening and every 2 cycles * For Partial Response (PR) or Complete Response (CR), changes in tumor measurements must be confirmed by repeat studies no less than 4 weeks after the criteria for response are first met (RECIST 1.1 criteria) * For Stable Disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum of 12 weeks after study entry

  12-18 weeks

Secondary Outcomes (4)

• Safety: combination of everolimus and sorafenib

  12-18 weeks

• Progression-free Survival (PFS)

  12-18 weeks

• Time-to-Progression (TTP)

  12-18 weeks

• Clinical Benefit rate

  12-18 weeks

Study Arms (2)

Everolimus/Sorafenib

EXPERIMENTAL

Patients will be stratified by current smoking status (smoker: yes or no0, for each smoking stratum patients will be randomized in a 2:1 ratio

Drug: Everolimus and sorafenib

Sunitinib

ACTIVE COMPARATOR

* Sunitinib is the concurrent control group * Patients will be stratified by current smoking status (smoker: yes or no), for each smoking stratum patients will be randomized in a 2:1 ratio

Drug: Sunitinib monotherapy

Interventions

Everolimus and sorafenib DRUG

* Starting doses: everolimus 5 mg daily and sorafenib 400 mg BID - taken fasting, no food 1 hour before or 2 hours after dosing * Everolimus and sorafenib are dosed continuously (Note: everolimus and sorafenib are typically dosed in 28 day cycles, and sunitinib is typically dosed in 42 day cycles; for the purposes of this protocol to keep timing consistent, a cycle will be defined as 42 days of therapy)

Everolimus/Sorafenib

Sunitinib monotherapy DRUG

Starting dose: sunitinib 50 mg daily 4 weeks on, 2 weeks off - taken fasting, no food 1 hour before or 2 hours after dosing (Note: sunitinib is typically dosed in 42 day cycles described above: 28 days treatment, 14 days off. For the purposes of this protocol, to keep timing consistent, a cycle will be defined as 42 days of therapy)

Sunitinib

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically- or cytologically-confirmed renal cell carcinoma, which is unresectable or metastatic and of any of the following histologies: clear cell, papillary, chromophobic, oncocytic, unclassified, or mixed. A component of clear cell histology must be present. Tumors with pure collecting duct histology are not eligible.
• Cytoreductive nephrectomy is allowed but not required
• Evidence of RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥ 10 mm with spiral CT scan)
• Male or female at least 18 years old
• Female patients must be either surgically sterile or postmenopausal, or if of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment and agree to use effective barrier contraception during the period of therapy, and for 3 months after the end of treatment/end of participation in the study. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy, and for 3 months after the end of treatment/end of participation in the study.
• The definition of effective contraception will be based on the judgment of the investigator.
• ECOG performance status 0-1
• Adequate bone marrow function:
• ANC ≥ 1500/uL
• platelet count ≥ 100,000/uL
• hemoglobin ≥ 9.0 g/dL
• Adequate hepatic function:
• Total bilirubin ≤ 1.5 X ULN
• AST (SGOT) ≤ 2.5 X ULN

You may not qualify if:

• Collecting duct renal cell carcinoma is excluded. Transitional cell carcinoma of the renal pelvis is excluded.
• Prior systemic regimens for renal cell carcinoma (neoadjuvant therapy is acceptable as long as it did not include sunitinib, sorafenib, everolimus, or temsirolimus). A prior therapy which was started and stopped after no more than four weeks of therapy will not constitute a prior systemic regimen.
• Prior surgery, radiation therapy, or systemic therapy for renal cell carcinoma within 4 weeks of starting study treatment.
• History of or known brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan (evaluation for CNS disease is required to be performed for eligibility).
• Any of the following within 6 months prior to study drug administration: myocardial infarction, unstable or severe angina, coronary or peripheral artery bypass graft, NYHA functional Class II, III, IV congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Ejection fraction lower than institutional lower limit of normal by echocardiogram or MUGA.
• Hypertension that is unable to be controlled with medications to a blood pressure of ≤ 150/90.
• Hypothyroidism that is unable to be controlled with medications such that FT4 is outside of normal limits.
• QTc prolongation (QTc interval ≥ 480 msecs) or any other clinically significant ECG abnormalities.
• Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness (because of the immunosuppressive effects of therapy). Testing for HIV in the absence of a history or symptoms is not required.
• Hepatitis B or C (because of the risk of reactivation). The following serologies are acceptable for enrollment: HBsAg-/anti-HBc-/anti-HBs-; HBsAg-/anti-HBc+/anti-HBs+; HBsAg-/anti-HBc-/anti-HBs+. The following serologies are not acceptable for enrollment: HBsAg+/anti-HBc+(IgM+/-)/anti-HBs-. If the following serologies are obtained, additional testing will be required to ascertain the patient's hepatitis B status: HBsAg-/anti-HBc+/anti-HBs-.
• "Currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered to have a less than 30% risk of relapse.
• Current treatment on another clinical trial.
• Pregnant or breastfeeding.
• Chronic treatment with systemic steroids or other immunosuppressive agent.

Sponsors & Collaborators

• Andrea Harzstark: lead
• Novartis: collaborator

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Everolimus; Sorafenib

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Andrea Harzstark, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor, UCSF Helen Diller Cancer Center

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 11, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: April 1, 2016
• Last Updated: April 8, 2013

Record last verified: 2013-04