Evaluate Safety and Tolerability in Dose Escalation of Sorafenib in Advanced Renal Cell Cancer

NCT01189370 | Completed Phase 2 Results DMC

• 1 other identifier: 11277
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether an increase in the dose of sorafenib when given over five instead of 7 days/week, will result in an improvement of the response rate (degree of shrinkage of your cancer) and an improvement in the length of time that sorafenib will control your cancer, without causing a significant increase in side effects.

Conditions

Renal Cell Cancer

Keywords

carcinoma, renal cell; kidney; cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Could Tolerate Each Dose Level

  Tolerability will be defined as successful completion of the dose level without experiencing Grade 3 or 4 toxicity.

  12 weeks

Secondary Outcomes (1)

• Overall Number of Participants That Had Disease Progression on Study

  26 months

Study Arms (1)

Intra-Patient Dose Escalation: Sorafenib

EXPERIMENTAL

All patients will receive a starting dose of sorafenib 400 mg by mouth twice daily. At four weeks, all patients who have not experienced Grade 3 or 4 toxicity will undergo dose escalation using a treatment schedule of days 1-5 days of each week. Doses will continue to be escalated every 4 weeks depending on tolerability and tumor response.

Drug: sorafenib

Interventions

sorafenib DRUG

Dose Level: 1. 400mg twice daily, continuous. 2. 600mg twice daily, days 1-5 of each week. 3. 800mg twice daily, days 1-5 of each week.

Also known as: BAY 43-9006, Nexavar®

Intra-Patient Dose Escalation: Sorafenib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0 grams per deciliter (g/dl)
• Absolute neutrophil count (ANC)≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• and aspartate aminotransferase (AST) ≤ 2.5 times the ULN (≤ 5 x ULN for patients with liver involvement)
• Creatinine \< 1.5 times ULN
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to of treatment.
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study. Men should use adequate birth control for at least three months after the last administration of sorafenib.
• Ability to understand and willing to sign written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• International normalized ratio (INR) \< 1.5 or a prothrombin time/partial prothrombin time (PT/PTT) within normal limits unless receiving anti-coagulation treatment with an agent such as warfarin or heparin. These patients may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• Must have histologically or cytologically confirmed renal cell carcinoma that is metastatic (M1). Patients with unresectable primary tumor (but MO) are also eligible.
• Must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension. Soft tissue disease that has been radiated in the 2 months prior to registration is not assessable as measurable disease. Soft tissue disease within a prior radiation field must have progressed to be considered assessable. X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration. X-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration.

You may not qualify if:

• Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA). Must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within past 6 months.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Patients who have received prior sorafenib are ineligible.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B/C.
• Active clinically serious infection \> CTCAE Grade 2.
• Thrombosis or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. Patients with renal or caval thrombosis related to the primary renal tumor would not be excluded and are eligible.
• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• Known or suspected allergy to sorafenib or any agent given in the course of this trial.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Bayer: collaborator

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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)

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

Results Point of Contact

• Title: Dr. Peter Van Velduizen
• Organization: University of Kansas Cancer Center

SWILLIAM@kumc.edu

913-945-5059

Study Officials

• Stephen Williamson, MD

  The University of Kansas - Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 26, 2010
• Study Start: June 1, 2008
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: June 1, 2017
• Results First Posted: June 1, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)