Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma

This study has been terminated.
(The study was closed to enrollment when it became clear that enrollment was too slow to complete the full enrollment target within the time frame allowed.)
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:
NCT00557830
First received: November 9, 2007
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC.

The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Sorafenib Escalated Dose
Drug: Sorafenib Standard Dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)

Resource links provided by NLM:


Further study details as provided by Accelerated Community Oncology Research Network:

Primary Outcome Measures:
  • Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. [ Time Frame: Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment. ] [ Designated as safety issue: No ]
    Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.


Secondary Outcome Measures:
  • PFS Rate at 9, 13 and 17 Months [ Time Frame: PFS was to be measured at 9, 13, and 17 months. ] [ Designated as safety issue: No ]
    Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.

  • Overall Survival Rate [ Time Frame: Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death. ] [ Designated as safety issue: No ]
    Due to the early study closure and the small sample size, overall survival rate was not evaluated.

  • Changes From Baseline in Symptom Burden [ Time Frame: The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit. ] [ Designated as safety issue: No ]

    The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment.

    The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible).



Enrollment: 12
Study Start Date: January 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A: Escalated Dose
Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
Drug: Sorafenib Escalated Dose
Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
Other Name: Nexavar
Active Comparator: Group B: Standard Dose
Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Drug: Sorafenib Standard Dose
Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Other Name: Nexavar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years old.
  • Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid >50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent.
  • Karnofsky Performance Status of 50% or greater at study entry.
  • Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN.
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
  • Women of childbearing potential and sexually active men must agree to use adequate barrier contraception prior to study entry, for the duration of study participation, and for at least three months after the last administration of sorafenib.
  • INR < 1.5 or a PT/ PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin 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.
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

  • Prior systemic anticancer treatment for metastatic disease, including investigational therapy.
  • Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.
  • Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.
  • Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.
  • Hemodialysis or peritoneal dialysis.
  • Treatment with radiotherapy within 2 weeks of enrollment.
  • Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy.
  • Uncontrolled hypertension defined as SBP > 150 mmHg or DBP > 90 mmHg, despite optimal medical management.
  • Active clinically serious infection > Grade 2 per the CTCAE v3.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
  • Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the 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 administration of the first study drug dose.
  • Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Pregnancy or lactation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557830

Locations
United States, Arkansas
Clopton Clinic
Jonesboro, Arkansas, United States, 72401
United States, California
Wilshire Oncology Medical Group, Inc.
La Verne, California, United States, 91750
United States, Florida
Advanced Medical Specialties
Miami, Florida, United States, 33176
United States, Georgia
Northeast Georgia Cancer Care
Athens, Georgia, United States, 30607
Peachtree Hematology Oncology Consultants
Atlanta, Georgia, United States, 30309
Central Georgia Cancer Care
Macon, Georgia, United States, 31201
Northwest Georgia Oncology Centers
Marietta, Georgia, United States, 30060
United States, Illinois
Mid-Illinois Hematology and Oncology Associates, Ltd.
Normal, Illinois, United States, 61761
United States, Montana
Hematology Oncology Centers of the Northern Rockies
Billings, Montana, United States, 59101
United States, North Carolina
Gaston Hematology and Oncology
Gastonia, North Carolina, United States, 28054
United States, Oregon
Pacific Oncology, PC
Beaverton, Oregon, United States, 97006
United States, Pennsylvania
The Lancaster Cancer Center, Ltd
Lancaster, Pennsylvania, United States, 17605
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
Sponsors and Collaborators
Accelerated Community Oncology Research Network
Bayer
Investigators
Principal Investigator: Vasily Assikis, MD ACORN
  More Information

No publications provided

Responsible Party: Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier: NCT00557830     History of Changes
Other Study ID Numbers: AVJARCC0702
Study First Received: November 9, 2007
Results First Received: December 3, 2012
Last Updated: July 17, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Accelerated Community Oncology Research Network:
Renal Cell Carcinoma
Kidney Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014