Trial Outcomes & Findings for Etanercept and Gemcitabine in Patients With Advanced, Chemotherapy Naive Pancreatic Adenocarcinoma (NCT NCT00201838)

NCT ID: NCT00201838

Last Updated: 2017-11-30

Results Overview

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Percentages were calculated by a Kaplan Meier analysis.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

38 participants

Primary outcome timeframe

up to 6 months

Results posted on

2017-11-30

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental Group combination of gemcitabine and etanercept Gemcitabine: The starting dose will be 1000mg/m2 IV, weekly x 7 with a one week rest followed by weekly x 3 with one week rest for the remainder of treatment. Etanercept: Etanercept will be self administered subcutaneously by patients with injections 11 prepared by the investigational pharmacy, beginning 7 days prior to the first dose of gemcitabine and continued twice weekly for the duration of the study.	Control Group Patients received gemcitabine alone
Overall Study STARTED	30	8
Overall Study Treatment Cohort	30	8
Overall Study COMPLETED	30	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Etanercept and Gemcitabine in Patients With Advanced, Chemotherapy Naive Pancreatic Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interventional Arm n=30 Participants Patients received Etanercept with gemcitabine	Control Arm n=8 Participants Patients received Gemcitabine alone	Total n=38 Participants Total of all reporting groups
Age, Continuous	59 years n=93 Participants	59 years n=4 Participants	59 years n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	5 Participants n=4 Participants	19 Participants n=27 Participants
Sex: Female, Male Male	16 Participants n=93 Participants	3 Participants n=4 Participants	19 Participants n=27 Participants
Region of Enrollment United States	30 participants n=93 Participants	8 participants n=4 Participants	38 participants n=27 Participants
Metastatic Site Liver only	16 patients n=93 Participants	0 patients n=4 Participants	16 patients n=27 Participants
Metastatic Site Liver + other	10 patients n=93 Participants	6 patients n=4 Participants	16 patients n=27 Participants
Metastatic Site other site	4 patients n=93 Participants	2 patients n=4 Participants	6 patients n=27 Participants
ECOG Performance Status (PS) PS 0 (Fully active)	7 patients n=93 Participants	3 patients n=4 Participants	10 patients n=27 Participants
ECOG Performance Status (PS) PS 1 (Restricted in physical activity)	21 patients n=93 Participants	5 patients n=4 Participants	26 patients n=27 Participants
ECOG Performance Status (PS) PS 2 (Ambulatory and capable of selfcare)	2 patients n=93 Participants	0 patients n=4 Participants	2 patients n=27 Participants

PRIMARY outcome

Timeframe: up to 6 months

Population: 5 patients of the experimental group were non evaluable and 2 patients in the control group were non evaluable for disease progression.

Outcome measures

Outcome measures
Measure	Experimental Group n=25 Participants Patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine	Control Group n=6 Participants Patients received gemcitabine alone
Anti-tumor Effect as Measured by the Proportion of Patients Free of Disease-progression at Six Months After Treatment Initiation	28 percent of patients with PFS	14 percent of patients with PFS

SECONDARY outcome

Timeframe: up to 12 months

Population: 2 patients in the control group were non evaluable for disease response due to patient withdrawal and another no baseline imaging for comparison. 5 patients in experimental group were non evaluable for response.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Experimental Group n=25 Participants Patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine	Control Group n=6 Participants Patients received gemcitabine alone
Number of Patients With Response Partial Response	12 percentage of patients	17 percentage of patients
Number of Patients With Response Stable Disease	32 percentage of patients	50 percentage of patients

SECONDARY outcome

Timeframe: Up to 12 months

Population: All evaluable patients

A clinical benefit was defined by the improvement of at least one parameter over at least 4 weeks, without worsening of any other parameter (change in weight, ECOG performance status, Quality of life).

Outcome measures

Outcome measures
Measure	Experimental Group n=15 Participants Patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine	Control Group n=2 Participants Patients received gemcitabine alone
Percentage of Patients With Clinical Benefit Response	33 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: up to 1 year

Population: all evaluable patients

Median survival is defined as the time of initiation of the first dose of intervention to the date of death

Outcome measures

Outcome measures
Measure	Experimental Group n=29 Participants Patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine	Control Group n=8 Participants Patients received gemcitabine alone
Median Overall Survival Rates for Patients	5.43 months Interval 3.3 to 10.23	8.1 months Interval 3.1 to 20.4

SECONDARY outcome

Timeframe: up to 6 months

Population: Compare CBR with responders and non responders with available blood samples.

Outcome measures

Outcome measures
Measure	Experimental Group n=6 Participants Patients received etanercept 25mg subcutaneously twice-weekly with gemcitabine	Control Group n=7 Participants Patients received gemcitabine alone
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines NFkB	6.03 delta Ct values Standard Deviation 4.62	4.38 delta Ct values Standard Deviation 3.13
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines IL-10	28.04 delta Ct values Standard Deviation 1.93	26.85 delta Ct values Standard Deviation 1.38
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines IL-1b	16.2 delta Ct values Standard Deviation 7.29	13.07 delta Ct values Standard Deviation 7.44
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines IL-12	35.66 delta Ct values Standard Deviation 1.86	36.11 delta Ct values Standard Deviation 1.24
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines TNF	26.66 delta Ct values Standard Deviation 3.84	27.26 delta Ct values Standard Deviation 4.82
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines IFN	28.7 delta Ct values Standard Deviation 2.13	28.63 delta Ct values Standard Deviation 1.55
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines IL-6	29.25 delta Ct values Standard Deviation 1.31	29.29 delta Ct values Standard Deviation 1.39

Adverse Events

Experimental Group

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Miguel Villalona-Calero, MD

The Ohio State Unversity Comprehensive Cancer Center

Phone: 614-293-5484

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Experimental Group n=29 participants at risk Patients in the experimental group received etancercept 25 mg subcutaneously twice-weekly with gemcitabine.	Control Group n=8 participants at risk Patients in the control cohort received gemcitabine alone.
Blood and lymphatic system disorders Anemia	69.0% 20/29 • Number of events 20 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	87.5% 7/8 • Number of events 7 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Investigations Leukopenia	41.4% 12/29 • Number of events 12 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	75.0% 6/8 • Number of events 6 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Investigations Neutropenia	31.0% 9/29 • Number of events 9 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	37.5% 3/8 • Number of events 3 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Injury, poisoning and procedural complications Thrombocytopenia	27.6% 8/29 • Number of events 8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	62.5% 5/8 • Number of events 5 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Blood and lymphatic system disorders Febrile Neutropenia	3.4% 1/29 • Number of events 1 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
General disorders Fatigue	48.3% 14/29 • Number of events 14 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	62.5% 5/8 • Number of events 5 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Nausea	48.3% 14/29 • Number of events 14 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	75.0% 6/8 • Number of events 6 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Nervous system disorders Dysgeusia	41.4% 12/29 • Number of events 12 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	25.0% 2/8 • Number of events 2 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Constipation	31.0% 9/29 • Number of events 9 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	50.0% 4/8 • Number of events 4 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Vomiting	27.6% 8/29 • Number of events 8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	50.0% 4/8 • Number of events 4 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Investigations Transaminases	27.6% 8/29 • Number of events 8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	37.5% 3/8 • Number of events 3 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Diarrhea	24.1% 7/29 • Number of events 7 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	12.5% 1/8 • Number of events 1 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Mucositis	6.9% 2/29 • Number of events 2 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Vascular disorders Edema	6.9% 2/29 • Number of events 2 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Gastrointestinal disorders Dry mouth	6.9% 2/29 • Number of events 2 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Skin and subcutaneous tissue disorders Alopecia	6.9% 2/29 • Number of events 2 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	12.5% 1/8 • Number of events 1 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
Skin and subcutaneous tissue disorders Injection reaction	3.4% 1/29 • Number of events 1 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.
General disorders Chills	3.4% 1/29 • Number of events 1 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.	0.00% 0/8 Toxicities were graded according to the NCI Common Toxicity Criteria version 3.0. One patient was not evaluable for toxicity in the Experimental Group.