Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

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.

Sorafenib Escalated 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.

Sorafenib Standard Dose

Vasily Assikis, MD

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.

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

Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)

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.

Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.

Due to the early study closure and the small sample size, overall survival rate was not evaluated.

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).

Bayer

Accelerated Community Oncology Research Network

Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.

After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for \< 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).

Screening Treatment Phase

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.

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.

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 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.

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.

Group B: Standard Dose

Total

Randomization Phase

Age Continuous

Female (Screening Treatment Phase)

Male (Screening Treatment Phase)

Female (Randomization Phase)

Male (Randomization Phase)

Sex/Gender, Customized

United States

Region of Enrollment

United States (Screening Treatment Phase)

United States (Randomization Phase)

Region of Enrollment, Customized

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.

Vice President of Scientific Affairs

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

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

PFS Rate at 9, 13 and 17 Months

Overall Survival Rate

Hives (Welts)-Baseline

Hives (Welts)-Post-BL

Sinus Problem-Baseline

Sinus Problem-Post-BL

Chest Pain-Baseline

Chest Pain-Post-BL

Rapid Heart Beat-Baseline

Rapid Heart Beat-Post-BL

Swelling-Baseline

Swelling-Post-BL

Constitutional Chills-Baseline

Constitutional Chills-Post-BL

Fatigue-Baseline

Fatigue-Post-BL

Fever-Baseline

Fever-Post-BL

Weight Gain-Baseline

Weight Gain-Post-BL

Weight Loss-Baseline

Weight Loss-Post-BL

Change In Taste-Baseline

Change In Taste-Post-BL

Difficulty Hearing-Baseline

Difficulty Hearing-Post-BL

Dry Mouth-Baseline

Dry Mouth-Post-BL

Mouth Sores/Ulcers-Baseline

Mouth Sores/Ulcers-Post-BL

Sore Throat-Baseline

Sore Throat-Post-BL

Trouble Swallowing-Baseline

Trouble Swallowing-Post-BL

Day Sweat-Baseline

Day Sweat-Post-BL

Hot Flashes/Flushes-Baseline

Hot Flashes/Flushes-Post-BL

Night Sweat-Baseline

Night Sweat-Post-BL

Reduced Sexual Enjoyment-Baseline

Reduced Sexual Enjoyment-Post-BL

Dry Eyes-Baseline

Dry Eyes-Post-BL

Tearing-Baseline

Tearing-Post-BL

Trouble Seeing-Baseline

Trouble Seeing-Post-BL

Constipation-Baseline

Constipation-Post-BL

Decrease in Appetite-Baseline

Decrease in Appetite-Post-BL

Diarrhea-Baseline

Diarrhea-Post-BL

Heartburn-Baseline

Heartburn-Post-BL

Increase in Appetite-Baseline

Increase in Appetite-Post-BL

Nausea-Baseline

Nausea-Post-BL

Vomiting-Baseline

Vomiting-Post-BL

Menstrual Pain/Cramping-Baseline

Menstrual Pain/Cramping-Post-BL

Problem with Urination-Baseline

Problem with Urination-Post-BL

Vaginal Bleeding-Baseline

Vaginal Bleeding-Post-BL

Vaginal Discharge-Baseline

Vaginal Discharge-Post-BL

Vaginal Dryness-Baseline

Vaginal Dryness-Post-BL

Vaginal Itching-Baseline

Vaginal Itching-Post-BL

Bleeding-Baseline

Bleeding-Post-BL

Bruising-Baseline

Bruising-Post-BL

New Lump/Mass-Baseline

New Lump/Mass-Post-BL

Breast Tenderness-Baseline

Breast Tenderness-Post-BL

Dry Skin-Baseline

Dry Skin-Post-BL

Hair Loss-Baseline

Hair Loss-Post-BL

Itching-Baseline

Itching-Post-BL

Nails Change-Baseline

Nails Change-Post-BL

Nipple Discharge-Baseline

Nipple Discharge-Post-BL

Rash-Baseline

Rash-Post-BL

Joint Pain-Baseline

Joint Pain-Post-BL

Muscle Aches-Baseline

Muscle Aches-Post-BL

Weakness of Body Parts-Baseline

Weakness of Body Parts-Post-BL

Burning Sensation in Hands or Feet-Baseline

Burning Sensation in Hands or Feet-Post-BL

Changes From Baseline in Symptom Burden

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions. The median progression free survival is the parameter used to describe PFS.

Median Progression Free Survival (PFS)

Treatment Phase

Spots Global Cancer Trial Database for sorafenib escalated dose