Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

TVEC and Preop Radiation for Sarcoma (4 ml Dose)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02453191
Recruitment Status : Active, not recruiting
First Posted : May 25, 2015
Results First Posted : June 17, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Varun Monga, MD, University of Iowa

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Soft Tissue Sarcoma
Interventions Drug: Talimogene Laherparepvec
Radiation: Radiotherapy
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment
Hide Arm/Group Description

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Period Title: Overall Study
Started 30
Completed 29
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Treatment
Hide Arm/Group Description

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
7 subjects enrolled in the Phase 1b portion, 23 subjects enrolled in the Phase 2 portion of the study
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants
61
(28 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
9
  30.0%
Male
21
  70.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
1
   3.3%
Not Hispanic or Latino
29
  96.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   3.3%
White
29
  96.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Hide Description A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.
Time Frame 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
7 participants enrolled in the Phase 1b portion (Talimogene Laherparepvec Dose 0) and completed treatment, radiation, and surgical resection.
Arm/Group Title Treatment
Hide Arm/Group Description:

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Primary Outcome
Title Phase 2: Number of Subjects With Pathologic Tumor Necrosis ≥ 95% Following Concurrent Radiation Therapy and Talimogene Laherparepvec.
Hide Description At the end of the neoadjuvant therapy, patients will undergo resection of the treated tumor. The percentage of post treatment tumor necrosis must be documented. The primary end point for this study is pathologic complete response (pCR), and is defined as ≥ 95% tumor necrosis following concurrent radiation therapy and talimogene laherparepvec.
Time Frame 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In all 30 patients were accrued on the study. 1 patient refused surgery, 29 patient specimens analyzed
Arm/Group Title Treatment
Hide Arm/Group Description:

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Participants Analyzed 29
Measure Type: Count of Participants
Unit of Measure: Participants
no neoplasm identified
1
   3.4%
95% or greater
6
  20.7%
75% to 89%
4
  13.8%
50% to 74%
6
  20.7%
25% to 49%
4
  13.8%
Less than 25%
4
  13.8%
90% to 94%
4
  13.8%
3.Secondary Outcome
Title Overall Response Rate (ORR) as Measured by RECIST
Hide Description Overall response rate (ORR) as measured by RECIST 1.1. Complete response is the disappearance of all target lesions.Partial response is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease is a decrease in the tumor size of < 30% or an increase of < 20%..
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects completed the Phase Ib and 2 portions of the study and were determined evaluable for assessment of overall response
Arm/Group Title Treatment
Hide Arm/Group Description:

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response
0
   0.0%
Progressive disease
9
  30.0%
Stable disease
20
  66.7%
Partial response
1
   3.3%
4.Secondary Outcome
Title Time to Disease Progression (TTP)
Hide Description TTP is defined as the time from enrollment until objective tumor progression including local and distant recurrences as measured by RECIST 1.1. Complete response is the disappearance of all target lesions.Partial response is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease is a decrease in the tumor size of < 30% or an increase of < 20%.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects enrolled in the trial and included in TTP analysis
Arm/Group Title Treatment
Hide Arm/Group Description:

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Progressed at 3 months
4
  13.3%
Progressed at 6 months
1
   3.3%
Progressed at 9 months
1
   3.3%
Progressed at 16 months
1
   3.3%
Progressed prior to surgery
5
  16.7%
No signs of disease recurrance
18
  60.0%
5.Secondary Outcome
Title Overall Survival Rate (OS) at 5 Years
Hide Description Subjects will be followed for overall survival rate (OS) at 5 years from the last enrollment
Time Frame 5 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description To further assess the safety of talimogene laherparepvec given concurrently with preoperative external beam radiation in sarcoma patients.Information regarding the occurrence of adverse events will be collected from the time the subject signs the informed consent form and throughout their participation in the study, including a period of 30 days after the last dose of study drug.
Time Frame 14 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All 30 enrolled subjects were assessed for AEs
Arm/Group Title Treatment
Hide Arm/Group Description:

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
30
 100.0%
Time Frame Information regarding the occurrence of adverse events was collected from the time the subject signed the informed consent form and throughout their participation in the study, through a period of 30 days after the last dose of study drug, up to 14 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment
Hide Arm/Group Description

talimogene laherparepvec in combination with radiotherapy

talimogene laherparepvec: talimogene laherparepvec

Radiotherapy: Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.

All-Cause Mortality
Treatment
Affected / at Risk (%)
Total   4/30 (13.33%)    
Hide Serious Adverse Events
Treatment
Affected / at Risk (%) # Events
Total   4/30 (13.33%)    
Cardiac disorders   
Ventricular arrhythmia  2  1/30 (3.33%)  1
Infections and infestations   
Infections and infestations - Other  1  1/30 (3.33%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/30 (3.33%)  1
1
Term from vocabulary, CTCAE v4.0
2
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment
Affected / at Risk (%) # Events
Total   30/30 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  21/30 (70.00%)  49
Cardiac disorders   
Heart failure  1  1/30 (3.33%)  1
Palpitations  1  1/30 (3.33%)  1
Pericardial effusion  1  1/30 (3.33%)  1
Sinus bradycardia  1  1/30 (3.33%)  2
Sinus tachycardia  1  4/30 (13.33%)  8
Ear and labyrinth disorders   
Ear pain  1  1/30 (3.33%)  2
Tinnitus  1  1/30 (3.33%)  9
Vertigo  1  2/30 (6.67%)  7
Eye disorders   
Eye disorders - Other, specify  1  1/30 (3.33%)  2
Photophobia  1  1/30 (3.33%)  5
Gastrointestinal disorders   
Abdominal distension  1  1/30 (3.33%)  1
Abdominal pain  1  5/30 (16.67%)  5
Bloating  1  1/30 (3.33%)  1
Constipation  1  8/30 (26.67%)  14
Diarrhea  1  9/30 (30.00%)  24
Dry mouth  1  4/30 (13.33%)  6
Dyspepsia  1  2/30 (6.67%)  2
Dysphagia  1  1/30 (3.33%)  2
Gastroesophageal reflux disease  1  1/30 (3.33%)  1
Gastrointestinal disorders - Other,  1  1/30 (3.33%)  1
Mucositis oral  1  1/30 (3.33%)  1
Nausea  1  16/30 (53.33%)  39
Toothache  1  1/30 (3.33%)  1
Vomiting  1  14/30 (46.67%)  28
General disorders   
Chills  1  18/30 (60.00%)  46
Edema limbs  1  12/30 (40.00%)  19
Fatigue  1  26/30 (86.67%)  71
Fever  1  12/30 (40.00%)  16
Flu like symptoms  1  14/30 (46.67%)  48
General disorders and administration site  1  1/30 (3.33%)  1
Infusion related reaction  1  1/30 (3.33%)  1
Injection site reaction  1  5/30 (16.67%)  10
Localized edema  1  3/30 (10.00%)  5
Malaise  1  4/30 (13.33%)  7
Non-cardiac chest pain  1  1/30 (3.33%)  3
Pain  1  18/30 (60.00%)  52
Immune system disorders   
Allergic reaction  1  1/30 (3.33%)  1
Immune system disorders - Other,  1  1/30 (3.33%)  1
Infections and infestations   
Infections and infestations - Other,  1  2/30 (6.67%)  2
Sinusitis  1  1/30 (3.33%)  1
Skin infection  1  2/30 (6.67%)  2
Wound infection  1  2/30 (6.67%)  3
Injury, poisoning and procedural complications   
Bruising  1  1/30 (3.33%)  1
Dermatitis radiation  1  26/30 (86.67%)  63
Fall  1  1/30 (3.33%)  1
Injury, poisoning and procedural  1  2/30 (6.67%)  4
Wound complication  1  1/30 (3.33%)  1
Wound dehiscence  1  2/30 (6.67%)  2
Investigations   
Alanine aminotransferase  1  6/30 (20.00%)  8
Alkaline phosphatase increased  1  4/30 (13.33%)  5
Carbon monoxide diffusing capacity  1  1/30 (3.33%)  1
Creatinine increased  1  3/30 (10.00%)  8
Lymphocyte count decreased  1  10/30 (33.33%)  30
Neutrophil count decreased  1  3/30 (10.00%)  3
Platelet count decreased  1  4/30 (13.33%)  4
Weight loss  1  6/30 (20.00%)  11
White blood cell decreased  1  2/30 (6.67%)  2
Metabolism and nutrition disorders   
Acidosis  1  1/30 (3.33%)  1
Anorexia  1  9/30 (30.00%)  16
Dehydration  1  3/30 (10.00%)  4
Hypercalcemia  1  8/30 (26.67%)  17
Hyperkalemia  1  5/30 (16.67%)  6
Hypernatremia  1  1/30 (3.33%)  1
Hypoalbuminemia  1  4/30 (13.33%)  7
Hypocalcemia  1  2/30 (6.67%)  3
Hypokalemia  1  2/30 (6.67%)  3
Hypomagnesemia  1  1/30 (3.33%)  1
Hyponatremia  1  7/30 (23.33%)  13
Hypophosphatemia  1  1/30 (3.33%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  5/30 (16.67%)  6
Back pain  1  3/30 (10.00%)  3
Generalized muscle weakness  1  3/30 (10.00%)  4
Muscle weakness upper limb  1  1/30 (3.33%)  1
Musculoskeletal and connective tissue  1  5/30 (16.67%)  6
Myalgia  1  5/30 (16.67%)  6
Neck pain  1  2/30 (6.67%)  3
Pain in extremity  1  12/30 (40.00%)  22
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumor pain  1  5/30 (16.67%)  6
Nervous system disorders   
Amnesia  1  1/30 (3.33%)  1
Dizziness  1  7/30 (23.33%)  15
Dysgeusia  1  5/30 (16.67%)  8
Headache  1  15/30 (50.00%)  26
Nervous system disorders - Other,  1  2/30 (6.67%)  2
Neuralgia  1  2/30 (6.67%)  3
Paresthesia  1  4/30 (13.33%)  6
Peripheral sensory neuropathy  1  4/30 (13.33%)  5
Tremor  1  1/30 (3.33%)  1
Psychiatric disorders   
Agitation  1  1/30 (3.33%)  2
Anxiety  1  5/30 (16.67%)  13
Delirium  1  2/30 (6.67%)  2
Depression  1  1/30 (3.33%)  2
Hallucinations  1  1/30 (3.33%)  1
Insomnia  1  3/30 (10.00%)  4
Renal and urinary disorders   
Bladder spasm  1  1/30 (3.33%)  1
Hematuria  1  2/30 (6.67%)  2
Proteinuria  1  1/30 (3.33%)  1
Renal and urinary disorders - Other,  1  3/30 (10.00%)  4
Urinary frequency  1  3/30 (10.00%)  3
Urine discoloration  1  1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  3/30 (10.00%)  3
Cough  1  7/30 (23.33%)  12
Dyspnea  1  4/30 (13.33%)  9
Hiccups  1  1/30 (3.33%)  2
Hoarseness  1  1/30 (3.33%)  1
Hypoxia  1  1/30 (3.33%)  2
Nasal congestion  1  2/30 (6.67%)  2
Pleuritic pain  1  1/30 (3.33%)  1
Productive cough  1  2/30 (6.67%)  2
Respiratory, thoracic and mediastinal  1  2/30 (6.67%)  2
Skin and subcutaneous tissue disorders   
Bullous dermatitis  1  1/30 (3.33%)  1
Dry skin  1  3/30 (10.00%)  3
Erythema multiforme  1  1/30 (3.33%)  1
Pain of skin  1  1/30 (3.33%)  1
Pruritus  1  11/30 (36.67%)  12
Rash maculo-papular  1  6/30 (20.00%)  6
Skin and subcutaneous tissue  1  6/30 (20.00%)  8
Skin hyperpigmentation  1  1/30 (3.33%)  1
Skin ulceration  1  1/30 (3.33%)  1
Vascular disorders   
Flushing  1  2/30 (6.67%)  2
Hypertension  1  6/30 (20.00%)  19
Hypotension  1  1/30 (3.33%)  1
Thromboembolic event  1  2/30 (6.67%)  2
Vascular disorders - Other, specify  1  1/30 (3.33%)  1
1
Term from vocabulary, CTCAE v4.0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Varun Monga, MD
Organization: University of Iowa
Phone: 319-384-9497
EMail: varun-monga@uiowa.edu
Layout table for additonal information
Responsible Party: Varun Monga, MD, University of Iowa
ClinicalTrials.gov Identifier: NCT02453191    
Other Study ID Numbers: 201504731 (4 milliliter dose)
First Submitted: April 28, 2015
First Posted: May 25, 2015
Results First Submitted: May 13, 2020
Results First Posted: June 17, 2020
Last Update Posted: November 12, 2020