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Randomized Phase II Adjuvant Chemotherapy ± FANG™ in Colorectal Carcinoma With Liver Metastases (FANG-CLM)

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: NCT01505166
Recruitment Status : Terminated (Terminated (Business Decision to pursue other indications))
First Posted : January 6, 2012
Results First Posted : May 1, 2018
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Colon Cancer
Interventions Biological: Vigil™ Vaccine
Drug: Placebo
Enrollment 3
Recruitment Details This study recruited patients with colorectal carcinoma with liver metastases following resection and had successful manufacturing of Vigil (minimum of 4 doses). Part 1 would enroll the first 6 patients (Vigil plus chemotherapy) and then Part 2 would randomize subsequent patients (Vigil plus chemotherapy or Placebo plus chemotherapy).
Pre-assignment Details 3 subjects were enrolled in Part 1 and completed Vigil plus chemotherapy. No other subjects were enrolled in Part 1 and also Part 2.
Arm/Group Title Vigil™ Vaccine (Part 1) - 6 Patient run-in Vigil™ (Part 2) Placebo (Part 2)
Hide Arm/Group Description

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Placebo: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Period Title: Overall Study
Started 3 0 0
Completed 3 [1] 0 0
Not Completed 0 0 0
[1]
"Completed" means subject had successful Vigil manufacturing and had been given all the doses.
Arm/Group Title Vigil™ Vaccine (Part 1) 6 Patient run-in Vigil™ (Part 2) Placebo (Part 2) Total
Hide Arm/Group Description

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Placebo: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Total of all reporting groups
Overall Number of Baseline Participants 3 0 0 3
Hide Baseline Analysis Population Description
Study closed to enrollment and Part 2 was not initiated.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 0 participants 0 participants 3 participants
0-15 Years
0
   0.0%
0
   0.0%
16-64 Years
2
  66.7%
2
  66.7%
65 Years and Older
1
  33.3%
1
  33.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 0 participants 0 participants 3 participants
Female
2
  66.7%
2
  66.7%
Male
1
  33.3%
1
  33.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 0 participants 0 participants 3 participants
White/Caucasian
3
 100.0%
3
 100.0%
Black/African American
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
Hispanic
0
   0.0%
0
   0.0%
Other
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Immune Analysis in Tumor Biopsy and Blood (Part 1)
Hide Description To evaluate and correlate Tumor Infiltrating Lymphocytes (TIL) in initial excised tumor and Enzyme-Linked ImmunoSorbent Spot (ELISPOT) responses to Vigil™ vaccine in blood of patients with CLM.
Time Frame Up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
3 subjects were enrolled in Part 1 and completed Vigil plus chemotherapy. However, TIL was not tested/collected so no correlation could be performed. Statistical analysis was not done. This study was terminated.
Arm/Group Title Vigil™ Vaccine (Part 1) - 6 Patient run-in
Hide Arm/Group Description:

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Percent of Patients Who Progressed After Treatment (Part 2)
Hide Description Response rate will also be evaluated in this study using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) (unidimensional measurement) of the tumor lesions are used in the RECIST criteria.The response in patients with measurable disease will be reported using standard outcome measures for clinical trials: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Any response to treatment (either PR or CR) requires two confirmatory staging at least 4 weeks apart. Patients will be evaluable for tumor response if measurable disease is present.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was for Part 2. No subjects were randomized in Part 2. This study was terminated.
Arm/Group Title Vigil™ (Part 2) Placebo (Part 2)
Hide Arm/Group Description:

Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Placebo: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Percent of Patients Who Survived After Treatment (Part 2)
Hide Description To determine and compare the overall survival rate in patients with CLM following resection +/- ablation with curative intent treated with sandwich or adjuvant chemotherapy and Vigil™ vaccine versus sandwich or adjuvant chemotherapy and placebo and compare with historical data.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was for Part 2. No subjects were randomized in Part 2. This study was terminated.
Arm/Group Title Vigil™ (Part 2) Placebo (Part 2)
Hide Arm/Group Description:

Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Placebo: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Other Pre-specified Outcome
Title Enzyme-Linked ImmunoSorbent Spot (ELISPOT) (Part 1)
Hide Description To determine if subjects will have a positive (defined as >10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until 30 days after last dose.
Time Frame Baseline, End of Treatment (30 days after last dose) up to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
3 subjects were enrolled in Part 1 and completed Vigil plus chemotherapy. After 12 months, all 3 subjects had positive ELISPOT response. Statistical analysis was not done. This study was terminated.
Arm/Group Title Vigil™ Vaccine (6 Patient run-in)
Hide Arm/Group Description:

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
ELISPOT-Positive After 12 months 3
ELISPOT-Negative After 12 months 0
5.Other Pre-specified Outcome
Title Number of Alive Subjects (Part 1)
Hide Description For Part 1, this was to determine the overall survival rate in patients with CLM following resection +/= ablation with curative intent treated with adjuvant chemotherapy and Vigil™ by following these patients up to 24 months.
Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
3 subjects were enrolled in Part 1 and completed Vigil plus chemotherapy. After 24 months, 2 subjects were still alive and 1 subject was dead. Statistical analysis was not done. This study was terminated.
Arm/Group Title Vigil™ Vaccine (Part 1) 6 Patient run-in
Hide Arm/Group Description:

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Overall Number of Participants Analyzed 3
Measure Type: Count of Participants
Unit of Measure: Participants
Alive after 24 months
2
  66.7%
Dead after 24 months
1
  33.3%
Time Frame [Not Specified]
Adverse Event Reporting Description At the time that the trial closed, only one subject had died. The other two were still alive. Three serious adverse events were reported during the same hospitalization for one subject.
 
Arm/Group Title Vigil™ Placebo Vigil™ Vaccine (6 Patient run-in)
Hide Arm/Group Description

Patients will receive 1 x 10^7 cells (Group A) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses (vaccine) starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Patients will receive placebo (Group B) via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days.

Placebo: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7 cells/injection; maximum of 12 vaccinations).

Vigil™ Vaccine: Patients will receive 1 x 10^7 cells (Group A) or placebo (Group B) via intradermal injection for a minimum of 5 doses and a maximum of 12 doses starting post-surgery Week 4-8 (C1W1D1) and continuing C1W3D1, C2W3D1, then every 28 days. Starting C1W4D1, all patients will receive modified FOLFOX6 (oxaliplatin 85 mg/m2 D1, l-leucovorin 200 mg/m2 D1, fluorouracil 400 mg/m2 IV bolus (or short infusion) D1, fluorouracil 2400 mg/m2 46 hours continuous infusion every 14 days x 6 cycles (1 cycle = 4 weeks).

All-Cause Mortality
Vigil™ Placebo Vigil™ Vaccine (6 Patient run-in)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/0      0/0      1/3 (33.33%)    
Show Serious Adverse Events Hide Serious Adverse Events
Vigil™ Placebo Vigil™ Vaccine (6 Patient run-in)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      0/0      1/3 (33.33%)    
Infections and infestations       
Urinary Tract Infection  1  0/0  0 0/0  0 1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders       
Fracture  1  0/0  0 0/0  0 1/3 (33.33%)  1
Vascular disorders       
Thromboembolic Event  1  0/0  0 0/0  0 1/3 (33.33%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vigil™ Placebo Vigil™ Vaccine (6 Patient run-in)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      0/0      3/3 (100.00%)    
General disorders       
Injection Site Reaction  1  0/0  0 0/0  0 3/3 (100.00%)  3
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Trials
Organization: Gradalis, Inc.
Phone: 2144428124
EMail: info@gradalisinc.com
Publications of Results:
Long-term followup of bi-shRNAfurin and GMCSF augmented autologous tumor cell immunotherapy treated colorectal cancer patients in phase I and IIa studies. Minal A. Barve, Anton M. Melnyk, Luisa Manning, Gladice Wallraven, Martin Birkhofer, and John J. Nemunaitis Journal of Clinical Oncology 2017 35:15_suppl, e15100-e15100
Other Publications:
Layout table for additonal information
Responsible Party: Gradalis, Inc.
ClinicalTrials.gov Identifier: NCT01505166     History of Changes
Other Study ID Numbers: CL-PTL 107
First Submitted: January 4, 2012
First Posted: January 6, 2012
Results First Submitted: February 15, 2018
Results First Posted: May 1, 2018
Last Update Posted: September 24, 2019