Trial Outcomes & Findings for Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab (NCT NCT00939627)

Last Updated: 2018-01-23

Results Overview

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)

Results posted on

2018-01-23

Participant Flow

Southeast Phase II Consortium (SEP2C) study enrolling participants at seven participating sites during August 2009 through October 2011.

Fifty-five patients were consented and assigned to a treatment arm; 3 withdrew before treatment. Fifty-two patients were treated on study. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.

Participant milestones

Participant milestones
Measure	Arm A - Cetuximab Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility..	Arm B - Cetuximab and Sorafenib Tosylate Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Overall Study STARTED	27	28
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	27	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A - Cetuximab Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility..	Arm B - Cetuximab and Sorafenib Tosylate Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Overall Study Disease Progression	16	12
Overall Study Adverse Event	6	7
Overall Study Death	0	2
Overall Study Withdrawal by Subject	2	4
Overall Study Other complicating disease	1	1
Overall Study Not compliant	2	0
Overall Study No off-tx reason given	0	2

Baseline Characteristics

Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A - Cetuximab n=27 Participants Patients were to receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=28 Participants Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21.	Total n=55 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Customized	59 years n=5 Participants	60 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	28 participants n=7 Participants	55 participants n=5 Participants

PRIMARY outcome

Timeframe: On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where either death or progression is an event, with censoring for non-progressed, non-expired patients at greater of off-study date or last known alive date.

Outcome measures

Outcome measures
Measure	Arm A - Cetuximab n=26 Participants Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=26 Participants Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Progression Free Survival (PFS)	3 months Interval 1.9 to 5.0	3.2 months Interval 1.8 to 4.2

SECONDARY outcome

Timeframe: On-treatment date to date of disease progression (assessed up to 3 years)

Population: All patients with best overall response data. Patients are excluded if best overall response data is missing or if the patient is not evaluable for best overall response.

Number of patients in each response category, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), \>=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), \>=20% increase in sum of longest diameter (LD) of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

Outcome measures

Outcome measures
Measure	Arm A - Cetuximab n=22 Participants Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=20 Participants Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Best Response Patients with Complete Response	0 participants	0 participants
Best Response Patients with Partial Response	1 participants	2 participants
Best Response Patients with Stable Disease	11 participants	10 participants
Best Response Patients with Progressive Disease	9 participants	8 participants
Best Response Patients Not Evaluable	4 participants	6 participants
Best Response Patients with Less Than Partial Response	1 participants	0 participants

SECONDARY outcome

Timeframe: On-study date to date of death from any cause (assessed up to 3 years)

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.

Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)

Outcome measures

Outcome measures
Measure	Arm A - Cetuximab n=26 Participants Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=26 Participants Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Overall Survival (OS)	9 months Interval 5.2 to 12.9	5.7 months Interval 4.2 to 10.8

SECONDARY outcome

Timeframe: On-study date to 30 days following final dose of study drug

Population: Total number of patients reported with any toxicity. Because not all patients experience a toxicity, and some experience more than one; the number of patients analyzed does not coincide with the number of patients on study.

Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death

Outcome measures

Outcome measures
Measure	Arm A - Cetuximab n=23 Participants Patients were to receive cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=24 Participants Patients received cetuximab 400 mg/m\^2 IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate 400 mg by mouth twice daily on days 1-21.
Number of Participants With Each Worst-Grade Toxicity Number of Patients with Worst-Grade Toxicity 1	6 participants	7 participants
Number of Participants With Each Worst-Grade Toxicity Number of Patients with Worst-Grade Toxicity 2	11 participants	4 participants
Number of Participants With Each Worst-Grade Toxicity Number of Patients with Worst-Grade Toxicity 3	5 participants	12 participants
Number of Participants With Each Worst-Grade Toxicity Number of Patients with Worst-Grade Toxicity 4	1 participants	1 participants
Number of Participants With Each Worst-Grade Toxicity Number of Patients with Worst-Grade Toxicity 5	0 participants	0 participants

SECONDARY outcome

Timeframe: Pre-therapy

Population: Due to an insufficient amount of tumor tissue available to complete planned analysis, this analysis was abandoned.

Formalin-fixed, paraffin-embedded (FFPE) tumors were collected. The FFPE tumors were to be evaluated for p16 expression using immunohistochemistry staining with antibody. Gene Expression Levels (positive when \>70% cells stained, otherwise negative) were to be described using frequencies.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-therapy, up to about 42 months (follow-up for overall survival)

Population: Data were not collected due to an insufficient amount of tumor tissue available.

Twelve immunomodulatory cytokines were selected based on previous a feasibility study and detected using multiplex Luminex bead assays from patient's plasma. One cytokines, HGF, was eliminated due to extremely low expression. Three representative cytokines, TGF-beta 1, IL-8 and VEGF were to be evaluated for association with survival due to clustering.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 3 years

Population: Data were not collected as The Quality of Life survey instrument was not completed by study participants..

Quality of Life Survey results.

Outcome measures

Outcome data not reported

Adverse Events

Arm A - Cetuximab

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Arm B - Cetuximab and Sorafenib Tosylate

Serious events: 10 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Jill Gilbert, M.D.

Vanderbilt Ingram Cancer Center

Phone: 615-343-4677

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A - Cetuximab n=26 participants at risk Patients were to receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility.	Arm B - Cetuximab and Sorafenib Tosylate n=27 participants at risk Patients received cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21.
Cardiac disorders Acute coronary syndrome	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Cardiac disorders Sinus tachycardia	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 2 • 2 years, 4 months All participants who received treatment.
Gastrointestinal disorders Dysphagia	7.7% 2/26 • Number of events 2 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
General disorders Death NOS	3.8% 1/26 • Number of events 1 • 2 years, 4 months All participants who received treatment.	11.1% 3/27 • Number of events 3 • 2 years, 4 months All participants who received treatment.
General disorders Infusion related reaction	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 2 • 2 years, 4 months All participants who received treatment.
Immune system disorders Anaphylaxis	3.8% 1/26 • Number of events 1 • 2 years, 4 months All participants who received treatment.	0.00% 0/27 • 2 years, 4 months All participants who received treatment.
Infections and infestations Esophageal infection	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Infections and infestations Lung infection	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Investigations Blood bilirubin increased	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Metabolism and nutrition disorders Anorexia	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Metabolism and nutrition disorders Dehydration	3.8% 1/26 • Number of events 1 • 2 years, 4 months All participants who received treatment.	7.4% 2/27 • Number of events 2 • 2 years, 4 months All participants who received treatment.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Musculoskeletal and connective tissue disorders Neck pain	3.8% 1/26 • Number of events 1 • 2 years, 4 months All participants who received treatment.	0.00% 0/27 • 2 years, 4 months All participants who received treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	3.8% 1/26 • Number of events 1 • 2 years, 4 months All participants who received treatment.	0.00% 0/27 • 2 years, 4 months All participants who received treatment.
Nervous system disorders Syncope	3.8% 1/26 • Number of events 2 • 2 years, 4 months All participants who received treatment.	0.00% 0/27 • 2 years, 4 months All participants who received treatment.
Psychiatric disorders Nervous system disorders - Other - related to pain meds	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.
Vascular disorders Hypertension	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 2 • 2 years, 4 months All participants who received treatment.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/26 • 2 years, 4 months All participants who received treatment.	3.7% 1/27 • Number of events 1 • 2 years, 4 months All participants who received treatment.