Trial Outcomes & Findings for Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (NCT NCT00557830)

Last Updated: 2013-07-18

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

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

Results posted on

2013-07-18

Participant Flow

13 community oncology sites across the US associated with the ACORN network participated in this study. Enrollment started in January 2008 and was closed in August 2008 due to the low rate of accrual and lack of funds beyond the current level of support from Bayer.

Informed consent was obtained from all subjects. All subjects underwent a screening phase that could last up to 4 weeks during which pre-study assessments were completed. Eligible subjects then underwent a screening treatment phase in which they received commercial sorafenib for 4 weeks.

Participant milestones

Participant milestones
Measure	Screening Treatment Phase 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).	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. 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 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. 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.
Screening Treatment Phase STARTED	12	0	0
Screening Treatment Phase COMPLETED	6	0	0
Screening Treatment Phase NOT COMPLETED	6	0	0
Treatment Phase STARTED	0	4	2
Treatment Phase COMPLETED	0	4	2
Treatment Phase NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Screening Treatment Phase 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).	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. 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 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. 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.
Screening Treatment Phase Withdrawal by Subject	1	0	0
Screening Treatment Phase Adverse Event	2	0	0
Screening Treatment Phase Unable to tolerate standard dose	3	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Screening Treatment Phase n=12 Participants 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).	Group A: Escalated Dose n=4 Participants 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 B: Standard Dose n=2 Participants 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.	Total n=18 Participants Total of all reporting groups
Age Continuous Screening Treatment Phase	62.2 years STANDARD_DEVIATION 10.99 • n=5 Participants	NA years STANDARD_DEVIATION NA • n=7 Participants	NA years STANDARD_DEVIATION NA • n=5 Participants	62.2 years STANDARD_DEVIATION 10.99 • n=4 Participants
Age Continuous Randomization Phase	NA years STANDARD_DEVIATION NA • n=5 Participants	66.0 years STANDARD_DEVIATION 6.38 • n=7 Participants	58.5 years STANDARD_DEVIATION 7.78 • n=5 Participants	63.5 years STANDARD_DEVIATION 7.18 • n=4 Participants
Sex/Gender, Customized Female (Screening Treatment Phase)	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Sex/Gender, Customized Male (Screening Treatment Phase)	9 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	9 Participants n=4 Participants
Sex/Gender, Customized Female (Randomization Phase)	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Sex/Gender, Customized Male (Randomization Phase)	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	NA participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	0 participants n=4 Participants
Region of Enrollment, Customized United States (Screening Treatment Phase)	12 participants n=5 Participants	NA participants n=7 Participants	NA participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment, Customized United States (Randomization Phase)	NA participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Screening Treatment Phase 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).	Group A: Escalated Dose n=4 Participants 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 B: Standard Dose n=2 Participants 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.
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete Response (CR)	—	0 Participants	0 Participants
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Partial Response (PR)	—	0 Participants	0 Participants
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Stable Disease (SD)	—	3 Participants	1 Participants
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Progressive Disease (PD)	—	1 Participants	1 Participants

SECONDARY outcome

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

Population: 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, the PFS rate at 9, 13, and 17 months were not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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).

Outcome measures

Outcome measures
Measure	Screening Treatment Phase n=12 Participants 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).	Group A: Escalated Dose n=4 Participants 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 B: Standard Dose n=2 Participants 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.
Changes From Baseline in Symptom Burden Sinus Problem-Baseline	1.1 units on a scale Standard Deviation 2.51	2.3 units on a scale Standard Deviation 3.86	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Memory Loss-Post-BL	0.3 units on a scale Standard Deviation 0.87	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Hives (Welts)-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Chest Pain-Baseline	0.1 units on a scale Standard Deviation 0.32	0.3 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Chest Pain-Post-BL	0.3 units on a scale Standard Deviation 0.56	0.4 units on a scale Standard Deviation 0.54	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Rapid Heart Beat-Baseline	0.8 units on a scale Standard Deviation 2.53	2 units on a scale Standard Deviation 4	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Rapid Heart Beat-Post-BL	0.3 units on a scale Standard Deviation 0.75	0.9 units on a scale Standard Deviation 1.2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Swelling-Baseline	0.3 units on a scale Standard Deviation 0.95	0.8 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Swelling-Post-BL	1 units on a scale Standard Deviation 2.28	0 units on a scale Standard Deviation 0.06	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Fever-Post-BL	0.9 units on a scale Standard Deviation 1.47	1.4 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Constipation-Baseline	0.1 units on a scale Standard Deviation 0.32	0.3 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Diarrhea-Post-BL	0.8 units on a scale Standard Deviation 0.88	1.1 units on a scale Standard Deviation 0.77	1.3 units on a scale Standard Deviation 1.88
Changes From Baseline in Symptom Burden Increase in Appetite-Post-BL	0.2 units on a scale Standard Deviation 0.48	0.1 units on a scale Standard Deviation 0.14	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Vaginal Itching-Post-BL	0.5 units on a scale Standard Deviation 0.51	0.2 units on a scale Standard Deviation 0.27	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Itching-Post-BL	1.7 units on a scale Standard Deviation 2.78	1.2 units on a scale Standard Deviation 0.85	0.1 units on a scale Standard Deviation 0.19
Changes From Baseline in Symptom Burden Rash-Post-BL	1.7 units on a scale Standard Deviation 3	1.1 units on a scale Standard Deviation 2.09	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Joint Pain-Baseline	1 units on a scale Standard Deviation 2.16	1 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Daytime Sleepiness-Baseline	0.5 units on a scale Standard Deviation 0.97	0.8 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Daytime Sleepiness-Post-BL	1.1 units on a scale Standard Deviation 1.52	1.9 units on a scale Standard Deviation 1.91	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dizziness/Lightheadedness-Baseline	0.2 units on a scale Standard Deviation 0.42	0.5 units on a scale Standard Deviation 0.58	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dizziness/Lightheadedness-Post-BL	0.4 units on a scale Standard Deviation 0.68	0.8 units on a scale Standard Deviation 0.78	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Thinking-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Thinking-Post-BL	0 units on a scale Standard Deviation 0.14	0.1 units on a scale Standard Deviation 0.25	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Headache-Baseline	0.1 units on a scale Standard Deviation 0.32	0.3 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Headache-Post-BL	0.5 units on a scale Standard Deviation 0.6	0.7 units on a scale Standard Deviation 0.55	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Pain-Post-BL	2 units on a scale Standard Deviation 2.51	2.6 units on a scale Standard Deviation 2.13	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Attend Paid Job-Post-BL	3.8 units on a scale Standard Deviation 3.98	3.7 units on a scale Standard Deviation 3.56	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Bathe or Dress-Baseline	0.2 units on a scale Standard Deviation 0.67	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Cook for Self-Post-BL	1.6 units on a scale Standard Deviation 2.45	2.6 units on a scale Standard Deviation 2.67	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Driving-Baseline	0.3 units on a scale Standard Deviation 1	0.8 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Function Normally-Post-BL	2.9 units on a scale Standard Deviation 2.8	3.8 units on a scale Standard Deviation 2.88	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Hard Work or Activity-Baseline	2.3 units on a scale Standard Deviation 2.87	1.3 units on a scale Standard Deviation 1.15	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Hard Work or Activity-Post-BL	3.9 units on a scale Standard Deviation 3.1	5.3 units on a scale Standard Deviation 3.52	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Light Work or Activity-Post-BL	2.6 units on a scale Standard Deviation 2.36	3.4 units on a scale Standard Deviation 2.65	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Site Up-Post-BL	0 units on a scale Standard Deviation 0.14	0.1 units on a scale Standard Deviation 0.25	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Walk-Baseline	0.8 units on a scale Standard Deviation 1.72	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Feeling I Would Be Better Off Dead-Post-BL	0.2 units on a scale Standard Deviation 0.47	0.2 units on a scale Standard Deviation 0.38	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nervous, Tense, Anxious-Baseline	1 units on a scale Standard Deviation 1.25	0.8 units on a scale Standard Deviation 0.96	1.5 units on a scale Standard Deviation 2.12
Changes From Baseline in Symptom Burden Wheezing-Post-BL	1 units on a scale Standard Deviation 2.29	2 units on a scale Standard Deviation 3.62	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Night Sweat-Post-BL	0.4 units on a scale Standard Deviation 1.3	1.1 units on a scale Standard Deviation 2.25	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Reduced Sexual Enjoyment-Baseline	0.2 units on a scale Standard Deviation 0.63	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weakness of Body Parts-Baseline	0.6 units on a scale Standard Deviation 1.07	1 units on a scale Standard Deviation 1.41	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Reduced Sexual Enjoyment-Post-BL	0.4 units on a scale Standard Deviation 1.08	0.9 units on a scale Standard Deviation 1.75	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weakness of Body Parts-Post-BL	1.8 units on a scale Standard Deviation 2.3	4 units on a scale Standard Deviation 2.74	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dry Eyes-Baseline	0.7 units on a scale Standard Deviation 2	1.5 units on a scale Standard Deviation 3	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dry Eyes-Post-BL	0.9 units on a scale Standard Deviation 1.49	1.4 units on a scale Standard Deviation 1.79	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Tearing-Baseline	1.1 units on a scale Standard Deviation 1.96	2.3 units on a scale Standard Deviation 2.63	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Walk-Post-BL	3.1 units on a scale Standard Deviation 3.19	3.4 units on a scale Standard Deviation 2.26	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Joint Pain-Post-BL	1.3 units on a scale Standard Deviation 2.14	0.9 units on a scale Standard Deviation 1.06	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Muscle Aches-Baseline	0.5 units on a scale Standard Deviation 1.08	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Muscle Aches-Post-BL	1.2 units on a scale Standard Deviation 2.06	0.8 units on a scale Standard Deviation 0.99	0.3 units on a scale Standard Deviation 0.35
Changes From Baseline in Symptom Burden Crying/Feeling Like Crying-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Burning Sensation in Hands or Feet-Baseline	0.8 units on a scale Standard Deviation 1.93	2 units on a scale Standard Deviation 2.83	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Burning Sensation in Hands or Feet-Post-BL	2.3 units on a scale Standard Deviation 3.12	2.6 units on a scale Standard Deviation 2.62	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Crying/Feeling Like Crying-Post-BL	0.2 units on a scale Standard Deviation 0.46	0.2 units on a scale Standard Deviation 0.36	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Hives (Welts)-Post-BL	1.2 units on a scale Standard Deviation 2.94	0.2 units on a scale Standard Deviation 0.38	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Sinus Problem-Post-BL	1.1 units on a scale Standard Deviation 1.89	2.4 units on a scale Standard Deviation 2.54	0.1 units on a scale Standard Deviation 0.11
Changes From Baseline in Symptom Burden Constitutional Chills-Baseline	0.2 units on a scale Standard Deviation 0.63	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Constitutional Chills-Post-BL	0.9 units on a scale Standard Deviation 1.69	0.8 units on a scale Standard Deviation 1.32	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Fatigue-Baseline	2.3 units on a scale Standard Deviation 2.54	3.8 units on a scale Standard Deviation 3.3	2 units on a scale Standard Deviation 2.83
Changes From Baseline in Symptom Burden Fatigue-Post-BL	2.7 units on a scale Standard Deviation 2.72	5 units on a scale Standard Deviation 3.22	0.5 units on a scale Standard Deviation 0.71
Changes From Baseline in Symptom Burden Fever-Baseline	0.4 units on a scale Standard Deviation 1.26	1 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weight Gain-Baseline	1.3 units on a scale Standard Deviation 2.75	1.8 units on a scale Standard Deviation 3.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weight Gain-Post-BL	0.3 units on a scale Standard Deviation 0.78	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weight Loss-Baseline	0.4 units on a scale Standard Deviation 1.26	1 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Weight Loss-Post-BL	0.7 units on a scale Standard Deviation 1.39	1.6 units on a scale Standard Deviation 2.14	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Change In Taste-Baseline	0.5 units on a scale Standard Deviation 1.27	1 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Change In Taste-Post-BL	0.8 units on a scale Standard Deviation 1.41	2.2 units on a scale Standard Deviation 1.81	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Difficulty Hearing-Baseline	0.7 units on a scale Standard Deviation 2.21	1.8 units on a scale Standard Deviation 3.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Difficulty Hearing-Post-BL	0.5 units on a scale Standard Deviation 1.24	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dry Mouth-Baseline	0.8 units on a scale Standard Deviation 2.04	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Dry Mouth-Post-BL	1.7 units on a scale Standard Deviation 1.5	2 units on a scale Standard Deviation 1.7	2.7 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Mouth Sores/Ulcers-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Mouth Sores/Ulcers-Post-BL	0.9 units on a scale Standard Deviation 1.53	0.6 units on a scale Standard Deviation 1.04	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Sore Throat-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Sore Throat-Post-BL	0.4 units on a scale Standard Deviation 0.63	0.5 units on a scale Standard Deviation 0.54	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Swallowing-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Swallowing-Post-BL	0.3 units on a scale Standard Deviation 0.62	0.3 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Day Sweat-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Day Sweat-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Hot Flashes/Flushes-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Hot Flashes/Flushes-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Night Sweat-Baseline	1.7 units on a scale Standard Deviation 3.65	4.3 units on a scale Standard Deviation 5.06	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Tearing-Post-BL	0.5 units on a scale Standard Deviation 1.36	1.2 units on a scale Standard Deviation 2.35	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Seeing-Baseline	0.4 units on a scale Standard Deviation 1.33	1 units on a scale Standard Deviation 2	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Seeing-Post-BL	1.6 units on a scale Standard Deviation 2.9	2 units on a scale Standard Deviation 3.37	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Constipation-Post-BL	0.2 units on a scale Standard Deviation 0.45	0.5 units on a scale Standard Deviation 0.71	0.3 units on a scale Standard Deviation 0.35
Changes From Baseline in Symptom Burden Decrease in Appetite-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Decrease in Appetite-Post-BL	0.8 units on a scale Standard Deviation 1.89	2.4 units on a scale Standard Deviation 2.87	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Diarrhea-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Heartburn-Baseline	0.7 units on a scale Standard Deviation 1.25	1.3 units on a scale Standard Deviation 1.89	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Heartburn-Post-BL	1.2 units on a scale Standard Deviation 1.67	2.7 units on a scale Standard Deviation 2.17	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Increase in Appetite-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nausea-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nausea-Post-BL	0.8 units on a scale Standard Deviation 1.11	1.4 units on a scale Standard Deviation 1.53	0.5 units on a scale Standard Deviation 0.71
Changes From Baseline in Symptom Burden Vomiting-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Vomiting-Post-BL	0.4 units on a scale Standard Deviation 0.86	1.1 units on a scale Standard Deviation 1.31	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Menstrual Pain/Cramping-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Menstrual Pain/Cramping-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Problem with Urination-Baseline	0.5 units on a scale Standard Deviation 1.08	1.3 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Problem with Urination-Post-BL	0.2 units on a scale Standard Deviation 0.48	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Vaginal Bleeding-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Bleeding-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Discharge-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Discharge-Post-BL	0.1 units on a scale Standard Deviation 0.14	0.1 units on a scale Standard Deviation 0.18	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Dryness-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Dryness-Post-BL	0 units on a scale Standard Deviation 0.07	0.1 units on a scale Standard Deviation 0.09	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Vaginal Itching-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Bleeding-Baseline	0.2 units on a scale Standard Deviation 0.63	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Bleeding-Post-BL	0.1 units on a scale Standard Deviation 0.17	0.1 units on a scale Standard Deviation 0.25	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Bruising-Baseline	0.2 units on a scale Standard Deviation 0.63	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Bruising-Post-BL	0.4 units on a scale Standard Deviation 1.35	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Memory Loss-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Numbness/Tingling-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Numbness/Tingling-Post-BL	0.7 units on a scale Standard Deviation 1.35	0.2 units on a scale Standard Deviation 0.19	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Trouble Sleeping at Night-Baseline	1.3 units on a scale Standard Deviation 2.06	1 units on a scale Standard Deviation 2	3 units on a scale Standard Deviation 4.24
Changes From Baseline in Symptom Burden Trouble Sleeping at Night-Post-BL	1.6 units on a scale Standard Deviation 1.81	2.5 units on a scale Standard Deviation 2.28	1 units on a scale Standard Deviation 1.41
Changes From Baseline in Symptom Burden Pain-Baseline	0.8 units on a scale Standard Deviation 1.14	1.3 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Attend Paid Job-Baseline	1.1 units on a scale Standard Deviation 2.42	2 units on a scale Standard Deviation 3.37	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Attend Social Activity-Baseline	0.6 units on a scale Standard Deviation 1.67	1.3 units on a scale Standard Deviation 2.5	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Attend Social Activity-Post-BL	1.8 units on a scale Standard Deviation 2.56	3 units on a scale Standard Deviation 2.68	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Bathe or Dress-Post-BL	1.3 units on a scale Standard Deviation 1.81	1.4 units on a scale Standard Deviation 1.69	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Cook for Self-Baseline	0.8 units on a scale Standard Deviation 2.33	1.8 units on a scale Standard Deviation 3.5	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Driving-Post-BL	1.2 units on a scale Standard Deviation 1.68	2.2 units on a scale Standard Deviation 2.09	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Function Normally-Baseline	2.3 units on a scale Standard Deviation 3.2	3.8 units on a scale Standard Deviation 4.35	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden New Lump/Mass-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Guilty-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden New Lump/Mass-Post-BL	0.2 units on a scale Standard Deviation 0.79	0.7 units on a scale Standard Deviation 1.38	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Breast Tenderness-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Breast Tenderness-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Dry Skin-Baseline	1.4 units on a scale Standard Deviation 2.99	2 units on a scale Standard Deviation 4	3 units on a scale Standard Deviation 4.24
Changes From Baseline in Symptom Burden Household Work-Baseline	1.6 units on a scale Standard Deviation 2.35	2.3 units on a scale Standard Deviation 3.3	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Household Work-Post-BL	2.8 units on a scale Standard Deviation 2.29	4.2 units on a scale Standard Deviation 2.84	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Light Work or Activity-Baseline	0.6 units on a scale Standard Deviation 1.13	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Run-Baseline	2 units on a scale Standard Deviation 2.98	0.7 units on a scale Standard Deviation 1.15	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Run-Post-BL	3.8 units on a scale Standard Deviation 3.96	5.9 units on a scale Standard Deviation 3.97	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Run Errands-Baseline	1.7 units on a scale Standard Deviation 3.32	3.8 units on a scale Standard Deviation 4.35	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Run Errands-Post-BL	2.5 units on a scale Standard Deviation 3	4.6 units on a scale Standard Deviation 3.73	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Dry Skin-Post-BL	2.5 units on a scale Standard Deviation 3.34	3.2 units on a scale Standard Deviation 2.72	0.2 units on a scale Standard Deviation 0.33
Changes From Baseline in Symptom Burden Hair Loss-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Hair Loss-Post-BL	1.2 units on a scale Standard Deviation 1.86	3.3 units on a scale Standard Deviation 1.9	0.5 units on a scale Standard Deviation 0.65
Changes From Baseline in Symptom Burden Itching-Baseline	1.1 units on a scale Standard Deviation 2.33	1.3 units on a scale Standard Deviation 2.5	3 units on a scale Standard Deviation 4.24
Changes From Baseline in Symptom Burden Sit Up-Baseline	0.2 units on a scale Standard Deviation 0.67	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Stay Out of Bed-Baseline	0.2 units on a scale Standard Deviation 0.67	0.5 units on a scale Standard Deviation 1	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Stay Out of Bed-Post-BL	0.5 units on a scale Standard Deviation 1.11	1.1 units on a scale Standard Deviation 1.66	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Guilty-Post-BL	0.2 units on a scale Standard Deviation 0.72	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Helpless-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Helpless-Post-BL	0.4 units on a scale Standard Deviation 0.94	0.8 units on a scale Standard Deviation 1.5	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Hopeless-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Hopeless-Post-BL	0.1 units on a scale Standard Deviation 0.43	0.4 units on a scale Standard Deviation 0.75	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling I Would Be Better Off Dead-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nails Change-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nails Change-Post-BL	0.7 units on a scale Standard Deviation 1.27	1.9 units on a scale Standard Deviation 1.62	0.1 units on a scale Standard Deviation 1.6
Changes From Baseline in Symptom Burden Nipple Discharge-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Nipple Discharge-Post-BL	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	NA units on a scale Standard Deviation NA All subjects in Group B are male.
Changes From Baseline in Symptom Burden Rash-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Worthless-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Feeling Worthless-Post-BL	0.3 units on a scale Standard Deviation 0.69	0.6 units on a scale Standard Deviation 1.13	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Lost Interest in People-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Lost Interest in People-Post-BL	0.4 units on a scale Standard Deviation 1.03	0.6 units on a scale Standard Deviation 1.13	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Lost Interest in Pleasurable Activities-Baseline	0.1 units on a scale Standard Deviation 0.32	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Lost Interest in Pleasurable Activities-Post-BL	0.5 units on a scale Standard Deviation 1.3	1.4 units on a scale Standard Deviation 2.14	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Nervous, Tense, Anxious-Post-BL	0.6 units on a scale Standard Deviation 0.87	0.9 units on a scale Standard Deviation 1.15	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Sad (Depressed)-Baseline	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Sad (Depressed)-Post-BL	0.5 units on a scale Standard Deviation 0.95	0.6 units on a scale Standard Deviation 1.25	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Worry-Baseline	1 units on a scale Standard Deviation 1.25	0.8 units on a scale Standard Deviation 0.96	1.5 units on a scale Standard Deviation 2.12
Changes From Baseline in Symptom Burden Worry-Post-BL	0.6 units on a scale Standard Deviation 1.05	0.8 units on a scale Standard Deviation 1.06	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Coughing-Baseline	1.6 units on a scale Standard Deviation 2.95	2 units on a scale Standard Deviation 4	3 units on a scale Standard Deviation 4.24
Changes From Baseline in Symptom Burden Coughing-Post-BL	1 units on a scale Standard Deviation 2.29	2.4 units on a scale Standard Deviation 3.79	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Shortness of Breath-Baseline	2.2 units on a scale Standard Deviation 2.86	3.3 units on a scale Standard Deviation 3.59	0 units on a scale Standard Deviation NA Only one subject provided a response at this timepoint; therefore, there is no SD.
Changes From Baseline in Symptom Burden Shortness of Breath-Post-BL	2.1 units on a scale Standard Deviation 2.7	4 units on a scale Standard Deviation 3.47	0 units on a scale Standard Deviation 0
Changes From Baseline in Symptom Burden Wheezing-Baseline	1.2 units on a scale Standard Deviation 2.57	2 units on a scale Standard Deviation 4	0.5 units on a scale Standard Deviation 0.71

POST_HOC outcome

Timeframe: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever occurred first

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.

Outcome measures

Outcome measures
Measure	Screening Treatment Phase n=12 Participants 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).	Group A: Escalated Dose n=4 Participants 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 B: Standard Dose n=2 Participants 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.
Median Progression Free Survival (PFS)	11.37 Months Interval 2.83 to 17.35	5.77 Months Interval 2.83 to 7.56	NA Months Interval 11.17 to Only 1 survival even occurred for Group B.

Adverse Events

Screening Treatment Phase

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Group A: Escalated Dose

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Group B: Standard Dose

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Screening Treatment Phase n=12 participants at risk 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).	Group A: Escalated Dose n=4 participants at risk 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 B: Standard Dose n=2 participants at risk 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.
Infections and infestations Bronchitis	0.00% 0/12 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Pneumonia	0.00% 0/12 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/12 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Deep vein thrombosis	0.00% 0/12 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	25.0% 1/4 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.	0.00% 0/2 • Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment. Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.

Other adverse events

Additional Information

Vice President of Scientific Affairs

Accelerated Community Oncology Research Network, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Bayer with such presentation, abstract, or manuscript at least 30 days prior to its presentation or submission for the sole purpose of allowing Bayer to redact confidential information and protect any existing or future patients. The Principal Investigator shall acknowledge Bayer contributions where appropriate.
Publication restrictions are in place

Restriction type: OTHER