Trial Outcomes & Findings for Study of Sorafenib/Cetuximab in Head and Neck Cancer (NCT NCT00815295)

Last Updated: 2014-12-08

Results Overview

The MTD is based upon dose-limiting (DLTs) experienced during Cycle 1 of treatment. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience DLT. Using Common Toxicity Criteria for Adverse EVents (CTCAE) version 3.0, DLTs are defined as any Grade 4 hematologic toxicity, or Grade 3 or 4 non-hematologic toxicity. A DLT will not be considered to have occurred in the case of a grade 3 or 4 allergic reaction due to cetuximab.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Cycle 1 (28 Days)

Results posted on

2014-12-08

Participant Flow

Patients with recurrent and/or metastatic squamous cell carinoma of the head and neck were enrolled between January 2008 and March 2011. The study was closed prematurely due to poor accrual.

Three patients were consented to the research study but withdrew consent prior to starting treatment. These patients are not included in the data presented.

Participant milestones

Participant milestones
Measure	Phase 1 - Dose Level 1 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg was administered orally twice daily.	Phase 1 - Dose Level 2 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 400 mg was administered orally twice daily.	Phase 2 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib was administered orally twice daily at the MTD from Phase I.
Overall Study STARTED	8	8	12
Overall Study COMPLETED	8	7	9
Overall Study NOT COMPLETED	0	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 - Dose Level 1 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg was administered orally twice daily.	Phase 1 - Dose Level 2 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 400 mg was administered orally twice daily.	Phase 2 Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib was administered orally twice daily at the MTD from Phase I.
Overall Study Cetuximab hypersensitivity reaction	0	1	3

Baseline Characteristics

Study of Sorafenib/Cetuximab in Head and Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 - Dose Level 1 n=8 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg was administered orally twice daily.	Phase 1 - Dose Level 2 n=8 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 400 mg was administered orally twice daily.	Phase 2 n=12 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib was administered orally twice daily at the MTD from Phase I.	Total n=28 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 7.8 • n=5 Participants	61.2 years STANDARD_DEVIATION 7.2 • n=7 Participants	62.8 years STANDARD_DEVIATION 12.3 • n=5 Participants	61.0 years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	20 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants	28 participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 Days)

Population: All patients treated on either dose level 1 or 2 as part of the phase I study.

Outcome measures

Outcome measures
Measure	Phase 1 n=16 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg or 400 mg was administered orally twice daily. The dose of sorafenib was escalated from 200 mg to 400 mg in successive 3+3 cohorts of patients to determine the maximum tolerated dose (MTD) of this regimen. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT).
Phase 1 - Maximum Tolerated Dose (MTD) of Sorafenib Administered With Cetuximab (400 mg/m2 Loading Dose Followed by 250 mg/m2 Weekly)	400 mg

PRIMARY outcome

Timeframe: 1 year

Population: Patients assigned to receive 400 mg of Sorafenib within the phase I or II component of the study are included in the analysis. 4 patients who had a Cetuximab hypersensitivity reaction on day 1 and then terminated treatment are excluded from the analyses.

The proportion of patients for whom the best overall response is complete response (CR), partial response (PR) or stable disease (SD). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disease) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. If follow-up assessments are not available, the best overall response is unevaluable.

Outcome measures

Outcome measures
Measure	Phase 1 n=16 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg or 400 mg was administered orally twice daily. The dose of sorafenib was escalated from 200 mg to 400 mg in successive 3+3 cohorts of patients to determine the maximum tolerated dose (MTD) of this regimen. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT).
Tumor Control Rate	43.8 percentage of participants Interval 19.8 to 70.1

SECONDARY outcome

Timeframe: 5 years

Time in months from the start of study treatment to date of death due to any cause. Median survival was estimated using a Kaplan-Meier curve and is the time point at which 50% of patients remain alive.

Outcome measures

Outcome measures
Measure	Phase 1 n=16 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg or 400 mg was administered orally twice daily. The dose of sorafenib was escalated from 200 mg to 400 mg in successive 3+3 cohorts of patients to determine the maximum tolerated dose (MTD) of this regimen. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT).
Median Survival	9.3 months Interval 1.4 to 14.0

SECONDARY outcome

Timeframe: 5 years

Time in months from the start of study treatment to the date of first progression (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, or death due to any cause. Per RECIST, a PD is indicated when there is at least a 20% increase in the sum of the longest diameters from target lesions relative to the smallest sum recorded since treatment is initiated. Median PFS was estimated using a Kaplan-Meier curve, and is the time at which 50% of patients remain alive without disease progression.

Outcome measures

Outcome measures
Measure	Phase 1 n=16 Participants Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg or 400 mg was administered orally twice daily. The dose of sorafenib was escalated from 200 mg to 400 mg in successive 3+3 cohorts of patients to determine the maximum tolerated dose (MTD) of this regimen. The MTD is the maximum dose level at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT).
Median Progression-Free Survival (PFS)	5.6 months Interval 1.4 to 7.8

SECONDARY outcome

Timeframe: 5 years

Population: QOL data were not consistently collected and can not be analyzed.

The outcome measure is the mean change in the Trial Outcome Index (TOI) between baseline and each follow-up assessment measured by the FACT-H\&N. The instrument consists of 39 items to assess physical (PWB), social and family (SWB), emotional (EWB), functional well-bing (FWB) and additional head and neck specific concerns (HNCS). Using a 5-point Likert type scale, responses to individual items range from 0 (not at all) to 4 (Very Much) with higher scores indicating better quality of life. The TOI is the sum of PWB (7 items), FWB (7 items) and HNCS scores (12 items). TOI ranges from 0 to 140.

Outcome measures

Outcome data not reported

Adverse Events

Phase 1 - Dose Level 1

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Phase 1 - Dose Level 2

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Phase 2

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1 - Dose Level 1 n=8 participants at risk Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 200 mg/m2 was administered orally twice daily.	Phase 1 - Dose Level 2 n=8 participants at risk Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib 400 mg/m2 was administered orally twice daily.	Phase 2 n=12 participants at risk Cetuximab was administered at the standard approved dose: 400 mg/m2 loading dose followed by 250 mg/m2 weekly. Sorafenib was administered orally twice daily at the MTD from Phase I.
Cardiac disorders Myocardial infarction	12.5% 1/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Nausea	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	12.5% 1/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Vomiting	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	12.5% 1/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders Death NOS	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	16.7% 2/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	8.3% 1/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Immune system disorders Cytokine release syndrome	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	8.3% 1/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Dehydration	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	12.5% 1/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	0.00% 0/8 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.	8.3% 1/12 The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Other adverse events

Additional Information

Neal Ready, MD

Duke University Medical Center

Phone: 919-668-6688

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place