Sorafenib in Treating Patients Who Are Undergoing Surgery for Metastatic Kidney Cancer

A Phase II Neoadjuvant Clinical Trial to Evaluate the Efficacy of BAY 43-9006 (Sorafenib) in Metastatic Renal Cell Carcinoma

Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib before and after surgery may be an effective treatment for kidney cancer. This phase II trial is studying how well sorafenib works in treating patients who are undergoing surgery for metastatic kidney cancer.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sorafenib tosylate; Procedure: therapeutic conventional surgery

Detailed Description

PRIMARY OBJECTIVES:

I. Efficacy of BAY 43-9006 (sorafenib tosylate) by evaluating response rate. II. Toxicities of BAY 43-9006 in metastatic renal cell carcinoma (RCC). III. Intraoperative and peri/postoperative safety of BAY 43-9006.

SECONDARY OBJECTIVES:

I. Time to progression. II. Duration of response. II. Overall Survival.

TERTIARY OBJECTIVES:

I. Tissue expression of VEGFR-2/phospho-VEGFR-2, PDGFR/phospho-PDGFR, FGFR/phospho-FGFR, ERK/phospho-ERK, RAF-1/phospho-RAF-1, p38/phospho-p38, Akt/phospho-Akt, P27, Ki67, TGF-alpha, and TUNEL pre- and post- therapy (optional studies).

II. Oligonucleotide analysis of tissue pre- and post-therapy (optional studies).

OUTLINE: This is a non-randomized study. Patients are sequentially assigned to 1 of 3 treatment groups.

GROUP I: Patients undergo cytoreductive nephrectomy on day 1. Patients then receive oral sorafenib twice daily on days 15-84.

GROUP II: Patients receive oral sorafenib twice daily on days 1-7. Patients undergo cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on days 22-84.

GROUP III: Patients receive oral sorafenib twice daily on days 1-28. Patients undergo cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily on days 43-84.

In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 45 patients (15 per treatment group) will be accrued for this study within 1 year.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically or cytologically confirmed metastatic clear cell RCC who are eligible for cytoreductive nephrectomy as agreed upon by Medical Oncology and Urology team members; patients with metastatic disease eligible for cytoreductive nephrectomy should have the following characteristics: resectable primary tumor (no gross adjacent organ invasion, no or minimal abdominal lymphadenopathy, no or minimal inferior vena caval involvement), bulk of metastatic disease within the primary tumor, absence of multiple liver metastases, no more than 2 organ sites involved with metastases
• Patients must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan
• ECOG performance status =< 1
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Hgb > 9.0 g/dL
• Total bilirubin =< 2.0 mg/dl
• Albumin > 3.0 g/dL
• Serum creatinine =< 2.0 mg/dl
• AST (SGOT) and/or ALT (SGPT) =< 2.5 x institutional upper limit of normal for subjects without evidence of liver metastases
• AST (SGOT) and/or ALT (SGPT) =< 5 X institutional upper limit of normal for subjects with documented liver metastases
• Female patients of childbearing potential must have a normal plasma beta human chorionic gonadotropin (beta-HCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect; however, patients will be eligible if their beta-HCG is elevated and is determined to be due to malignancy
• Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study
• Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy
• Patients must have ability to comply with study and/or follow-up procedures
• Prior biopsy material (blocks or unstained slides) must be available for comparison purposes

Exclusion Criteria:

• No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 5 years
• Patients must not have received any systemic anticancer therapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients must not be scheduled to receive another experimental drug while on this study; patients are permitted to be on concomitant bisphosphonates
• Patients who are incapable of swallowing pills are excluded from this study
• Patients must not have a primary brain tumor, any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke
• Patients must not have active acute infections that could be worsened by anticancer therapy or interfere with this study
• Patients must not have clinically significant cardiovascular disease, recent myocardial infarction (i.e. last 6 months), (unstable angina), New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac dysrhythmia requiring medication, or peripheral vascular disease (grade II or greater)
• Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
• Patients with uncontrolled hypertension > 140/90 are excluded from the study
• Patients must not have any history of bleeding diathesis; patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose coumadin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (cytoreductive nephrectomy and sorafenib tosylate); Patients undergo cytoreductive nephrectomy on day 1. Patients then receive oral sorafenib twice daily on days 15-84. In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.	Other: laboratory biomarker analysis; Correlative studies; Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN; Procedure: therapeutic conventional surgery; Undergo cytoreductive nephrectomy
Experimental: Group II (sorafenib tosylate and cytoreductive nephrectomy); Patients receive oral sorafenib twice daily on days 1-7. Patients undergo cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on days 22-84. In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.	Other: laboratory biomarker analysis; Correlative studies; Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN; Procedure: therapeutic conventional surgery; Undergo cytoreductive nephrectomy
Experimental: Group III (sorafenib tosylate and cytoreductive nephrectomy); Patients receive oral sorafenib twice daily on days 1-28. Patients undergo cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily on days 43-84. In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.	Other: laboratory biomarker analysis; Correlative studies; Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN; Procedure: therapeutic conventional surgery; Undergo cytoreductive nephrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of BAY 43-9006 by Evaluating Response Rate	Response rate (participants with response/total number participants) where number of participants with response evaluated using international criteria proposed by (RECIST) Committee of: Complete Response: Disappearance all target lesions; Partial Response (PR): > 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): > 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1 or > new lesions; Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.	Every 2 weeks during 4 week cycle

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Overall Response	Duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started), measured in days.	Following 10 weeks of treatment, followed every 2 weeks or until disease progression
Overall Survival	The number of participants surviving from baseline (treatment) to death due to any cause measured in days.	Up to 2 years
Time to Progression	Time, in weeks, after treatment until disease progresses. Repeat radiologic studies to evaluate disease progression or response after 10 weeks of BAY 43 9006 therapy.	Following 10 weeks of treatment or until disease progression

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Eric Jonasch, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 2, 2005
• First Submitted That Met QC Criteria: August 2, 2005
• First Posted (Estimate): August 4, 2005

Study Record Updates

• Last Update Posted (Actual): November 20, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2012-02920 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016672 (U.S. NIH Grant/Contract); N01CM62202 (U.S. NIH Grant/Contract); CDR0000438709; 2004-0516 (Other Identifier: M D Anderson Cancer Center); 6630 (Other Identifier: CTEP)