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

NCT00557830 | Terminated Phase 2 Results

• 1 other identifier: AVJARCC0702
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; Kidney Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.

  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.

  Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.

Secondary Outcomes (3)

• PFS Rate at 9, 13 and 17 Months

  PFS was to be measured at 9, 13, and 17 months.

• Overall Survival Rate

  Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.

• Changes From Baseline in Symptom Burden

  The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.

Study Arms (2)

Group A: Escalated Dose

ACTIVE COMPARATOR

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

Group B: Standard Dose

ACTIVE COMPARATOR

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

Interventions

Sorafenib Escalated Dose DRUG

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.

Also known as: Nexavar

Group A: Escalated Dose

Sorafenib Standard Dose DRUG

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.

Also known as: Nexavar

Group B: Standard Dose

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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Bayer: collaborator

Study Sites (13)

Clopton Clinic

Jonesboro, Arkansas, 72401, United States

Location

Wilshire Oncology Medical Group, Inc.

La Verne, California, 91750, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Northeast Georgia Cancer Care

Athens, Georgia, 30607, United States

Location

Peachtree Hematology Oncology Consultants

Atlanta, Georgia, 30309, United States

Location

Central Georgia Cancer Care

Macon, Georgia, 31201, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

Mid-Illinois Hematology and Oncology Associates, Ltd.

Normal, Illinois, 61761, United States

Location

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, 59101, United States

Location

Gaston Hematology and Oncology

Gastonia, North Carolina, 28054, United States

Location

Pacific Oncology, PC

Beaverton, Oregon, 97006, United States

Location

The Lancaster Cancer Center, Ltd

Lancaster, Pennsylvania, 17605, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The decision to close the study was made by the funder , Bayer HealthCare Pharmaceuticals, in collaboration with ACORN due to the low rate of accrual in light of study timelines and the lack of funds beyond the current level of support from Bayer.

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Accelerated Community Oncology Research Network, Inc.

mwalker@acorncro.com

Study Officials

• Vasily Assikis, MD

  Acorn Cardiovascular, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 14, 2007
• Study Start: January 1, 2008
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: July 18, 2013
• Results First Posted: July 18, 2013

Record last verified: 2013-07

Locations

US (13)