Trial Outcomes & Findings for External Beam Radiation With Intratumoral Injection of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma (NCT NCT00365872)

Last Updated: 2017-03-23

Results Overview

Immune responses in patients treated with EBRT and DCs: Transient immune response = response detected at only one time point; Robust immune response = response detected at least at two time points. An individual patient was considered a responder to tumor cell lysates (TCL) or survivin if at any time point the response in the interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay was higher than 30 spots per 2 X 10\^5 cells and in the proliferation assay higher than 3,000 counts per minute (CPM) and the response in IFN-γ ELISPOT or proliferation assays to TCL or Ad-surv was more than 2 standard deviations (SD) higher than the response to the corresponding control lysate or Ad-c at the same time point and 2 SD higher than the response to the same stimuli before start of the treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2017-03-23

Participant Flow

Patients with histologically confirmed large high grade soft-tissue sarcomas (STS) of the extremity/trunk/chest wall were enrolled to the study from 5/18/2006 to 2/19/2009. These patients had clinical stage T2N0M0 with a significant (\>50%) risk of progressing to distant metastases.

Participant milestones

Participant milestones
Measure	COHORT 1: EBRT + DC Injection + Resection Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	COHORT 2: EBRT + DC Injection + Resection Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	COHORT 3: EBRT + DC Injection + Resection Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.
Overall Study STARTED	5	6	6
Overall Study COMPLETED	5	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

External Beam Radiation With Intratumoral Injection of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	COHORT 1: EBRT + DC Injection + Resection n=5 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	COHORT 2: EBRT + DC Injection + Resection n=6 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	COHORT 3: EBRT + DC Injection + Resection n=6 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Total n=17 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Age, Continuous	35 years n=5 Participants	61 years n=7 Participants	68 years n=5 Participants	53 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Region of Enrollment United States	5 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	17 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: All evaluable participants available for follow-up at time of analysis.

Outcome measures

Outcome measures
Measure	EBRT + DC Injection + Resection n=17 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Single Arm - Cohort 2 DC injection # 4 given 48 hours prior to surgery	Single Arm - Cohort 3 DC injection # 4 given 72 hours prior to surgery
Overall Response Rate (ORR) Developed Tumor Specific Response	9 participants	—	—
Overall Response Rate (ORR) Transient Response	3 participants	—	—
Overall Response Rate (ORR) Robust Response	6 participants	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: All evaluable participants available for follow-up at time of analysis.

Toxicity assessment during combination external beam radiation therapy (EBRT)/DC neoadjuvant treatment. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria.

Outcome measures

Outcome measures
Measure	EBRT + DC Injection + Resection n=17 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Single Arm - Cohort 2 DC injection # 4 given 48 hours prior to surgery	Single Arm - Cohort 3 DC injection # 4 given 72 hours prior to surgery
Occurrence of Significant (>/= Grade 2) Toxicity	0 participants	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: All evaluable participants available for follow-up at time of analysis.

Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC).

Outcome measures

Outcome measures
Measure	EBRT + DC Injection + Resection n=17 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Single Arm - Cohort 2 DC injection # 4 given 48 hours prior to surgery	Single Arm - Cohort 3 DC injection # 4 given 72 hours prior to surgery
Occurrence of Postoperative Wound Complications	5 participants	—	—

SECONDARY outcome

Timeframe: 3 years

Population: All evaluable participants available for follow-up at time of analysis.

Participants who had no evidence of the disease for at least one year after the start of the treatment (time of follow-up); for at least 2 years, and for at least 3 years.

Outcome measures

Outcome measures
Measure	EBRT + DC Injection + Resection n=17 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Single Arm - Cohort 2 DC injection # 4 given 48 hours prior to surgery	Single Arm - Cohort 3 DC injection # 4 given 72 hours prior to surgery
Participants With No Evidence of Disease at Follow-up At One Year Follow-up	12 participants	—	—
Participants With No Evidence of Disease at Follow-up At Two Year Follow-up	6 participants	—	—
Participants With No Evidence of Disease at Follow-up At Three Year Follow-up	4 participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Participants evaluable for this measure

To identify the nodes to be excised, an injection with Indium 111 (radio active dye) labeled dendritic cells (of vaccine #4) was performed 1 to 3 days prior to surgery. Patients were evenly divided to be assigned to one of three cohorts: Cohort 1, 1 day before surgery; Cohort 2, 2 days before surgery; Cohort 3, 3 days before surgery. Vaccine #4 was labeled in order to evaluate how long dendritic cells need to travel to regional draining lymphatics. Tumor resection was not delayed by this.

Outcome measures

Outcome measures
Measure	EBRT + DC Injection + Resection n=5 Participants Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.	Single Arm - Cohort 2 n=4 Participants DC injection # 4 given 48 hours prior to surgery	Single Arm - Cohort 3 n=6 Participants DC injection # 4 given 72 hours prior to surgery
Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort	0 participants	4 participants	6 participants

Adverse Events

EBRT + DC Injection + Resection

Serious events: 5 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	EBRT + DC Injection + Resection n=17 participants at risk Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.
Skin and subcutaneous tissue disorders Wound complication, non-infectious - Possibly related	5.9% 1/17 • Number of events 1 • 3 years All participants
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue, Other - Unrelated	5.9% 1/17 • Number of events 1 • 3 years All participants
Skin and subcutaneous tissue disorders Dermatology/Skin, Other - Unrelated	5.9% 1/17 • Number of events 1 • 3 years All participants
Vascular disorders Peripheral arterial ischemia - Unrelated	5.9% 1/17 • Number of events 1 • 3 years All participants
Vascular disorders Thrombosis/thrombus/embolism - Unrelated	5.9% 1/17 • Number of events 1 • 3 years All participants
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, Wound - Probably related	5.9% 1/17 • Number of events 1 • 3 years All participants

Other adverse events

Other adverse events
Measure	EBRT + DC Injection + Resection n=17 participants at risk Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts for that injection only. Dendritic Cell (DC) Injections: DCs (10\^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration. Patients were assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery, Group 2 - DC injection # 4 given 48 hours prior to surgery, Group 3 - DC injection # 4 given 72 hours prior to surgery. Radiation was delivered 5 days per week (Monday-Friday). Complete Resection - Surgery for tumor removal: Tumors were surgically resected 3-6 weeks after the completion of EBRT.
General disorders Fatitue	5.9% 1/17 • 3 years All participants
General disorders Constitutional Symptoms - Other	23.5% 4/17 • 3 years All participants
General disorders Insomnia	17.6% 3/17 • 3 years All participants
General disorders Rigors/chills	11.8% 2/17 • 3 years All participants
Metabolism and nutrition disorders Weight loss	11.8% 2/17 • 3 years All participants
General disorders Fever (in the absence of neutropenia)	5.9% 1/17 • 3 years All participants
General disorders Pain - Other	64.7% 11/17 • 3 years All participants
General disorders Pain - Extremity-limb	47.1% 8/17 • 3 years All participants
General disorders Pain - Head/headache	23.5% 4/17 • 3 years All participants
General disorders Pain - Back	17.6% 3/17 • 3 years All participants
General disorders Pain - Joint	17.6% 3/17 • 3 years All participants
General disorders Pain - Abdomen NOS	5.9% 1/17 • 3 years All participants
General disorders Pain - Chest/thorax NOS	5.9% 1/17 • 3 years All participants
General disorders Pain - Stomach	5.9% 1/17 • 3 years All participants
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation - Radiation	17.6% 3/17 • 3 years All participants
Skin and subcutaneous tissue disorders Dermatology/Skin - Other	23.5% 4/17 • 3 years All participants
Skin and subcutaneous tissue disorders Dry skin	23.5% 4/17 • 3 years All participants
Skin and subcutaneous tissue disorders Injection site reaction/extravasation changes	17.6% 3/17 • 3 years All participants
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation - Chemoradiation	17.6% 3/17 • 3 years All participants
Skin and subcutaneous tissue disorders Rash/desquamation	11.8% 2/17 • 3 years All participants
Skin and subcutaneous tissue disorders Wound complication, non-infectious	11.8% 2/17 • 3 years All participants
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	5.9% 1/17 • 3 years All participants
Skin and subcutaneous tissue disorders Hyperpigmentation	5.9% 1/17 • 3 years All participants
Skin and subcutaneous tissue disorders Pruritus/itching	5.9% 1/17 • 3 years All participants
Skin and subcutaneous tissue disorders Rash: erythema multiforme	5.9% 1/17 • 3 years All participants
Gastrointestinal disorders Constipation	58.8% 10/17 • 3 years All participants
Gastrointestinal disorders Nausea	58.8% 10/17 • 3 years All participants
Gastrointestinal disorders Anorexia	29.4% 5/17 • 3 years All participants
Gastrointestinal disorders Diarrhea	17.6% 3/17 • 3 years All participants
Gastrointestinal disorders Vomiting	17.6% 3/17 • 3 years All participants
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	23.5% 4/17 • 3 years All participants
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	11.8% 2/17 • 3 years All participants
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	5.9% 1/17 • 3 years All participants
Metabolism and nutrition disorders AST, SGOT (serum glutamic oxaloacetic transaminase)	5.9% 1/17 • 3 years All participants
Metabolism and nutrition disorders Metabolic/Laboratory - Other	5.9% 1/17 • 3 years All participants
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	5.9% 1/17 • 3 years All participants
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	5.9% 1/17 • 3 years All participants
General disorders Mood alteration - Anxiety	17.6% 3/17 • 3 years All participants
General disorders Neurology - Other	17.6% 3/17 • 3 years All participants
Nervous system disorders Neuropathy: sensory	11.8% 2/17 • 3 years All participants
General disorders Dizziness	5.9% 1/17 • 3 years All participants
General disorders Mood alteration - Depression	5.9% 1/17 • 3 years All participants
Respiratory, thoracic and mediastinal disorders Cough	29.4% 5/17 • 3 years All participants
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other	11.8% 2/17 • 3 years All participants
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	5.9% 1/17 • 3 years All participants
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	5.9% 1/17 • 3 years All participants
Blood and lymphatic system disorders Hemoglobin	29.4% 5/17 • 3 years All participants
Blood and lymphatic system disorders Leukocytes (total WBC)	11.8% 2/17 • 3 years All participants
Blood and lymphatic system disorders Blood/Bone Marrow - Other	5.9% 1/17 • 3 years All participants
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	5.9% 1/17 • 3 years All participants
Blood and lymphatic system disorders Platelets	5.9% 1/17 • 3 years All participants
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	11.8% 2/17 • 3 years All participants
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	11.8% 2/17 • 3 years All participants
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-upper	5.9% 1/17 • 3 years All participants
Musculoskeletal and connective tissue disorders Myositis (inflammation/damage of muscle)	5.9% 1/17 • 3 years All participants
Blood and lymphatic system disorders Edema: limb	23.5% 4/17 • 3 years All participants
Blood and lymphatic system disorders Lymphatics - Other	5.9% 1/17 • 3 years All participants
Eye disorders Vision-Blurred vision	11.8% 2/17 • 3 years All participants
Eye disorders Ocular/Visual - Other	5.9% 1/17 • 3 years All participants
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	5.9% 1/17 • 3 years All participants
Immune system disorders Allergy/Immunology - other	5.9% 1/17 • 3 years All participants
Infections and infestations Infection with unknown ANC - Urinary tract NOS	5.9% 1/17 • 3 years All participants
Infections and infestations Infection with unknown ANC - Wound	5.9% 1/17 • 3 years All participants
Renal and urinary disorders Renal/Genitourinary - Other	5.9% 1/17 • 3 years All participants
Renal and urinary disorders Urinary frequency/urgency	5.9% 1/17 • 3 years All participants
Cardiac disorders Hypertension	5.9% 1/17 • 3 years All participants
Endocrine disorders Hot flashes/flushes	5.9% 1/17 • 3 years All participants
Vascular disorders Thrombosis/embolism (vascular access-related)	5.9% 1/17 • 3 years All participants

Additional Information

Scott J. Antonia, M.D., Ph.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-3883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place