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Vaccine Therapy and 1-MT in Treating Patients With Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT01042535
Recruitment Status : Completed
First Posted : January 5, 2010
Results First Posted : March 5, 2015
Last Update Posted : April 11, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Interventions Biological: adenovirus-p53 transduced dendritic cell (DC) vaccine
Drug: 1-methyl-d-tryptophan
Other: Laboratory biomarker analysis
Enrollment 44
Recruitment Details Participants were recruited at Moffitt Cancer Center from December 28, 2009, through February 11, 2014.
Pre-assignment Details  
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Period Title: Overall Study
Started 44
Completed 36
Not Completed 8
Reason Not Completed
disease progression prior to treatment             3
disease progression during treatment             3
complications from other disease             2
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Baseline Participants 44
Hide Baseline Analysis Population Description
All participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
<=18 years
0
   0.0%
Between 18 and 65 years
36
  81.8%
>=65 years
8
  18.2%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 44 participants
52.68
(27 to 73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants
Female
40
  90.9%
Male
4
   9.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 44 participants
44
1.Primary Outcome
Title Phase 1 - Maximum Tolerated Dose (MTD) in Milligrams (mg)
Hide Description MTD of 1-methyl-d-tryptophan (indoximod) given by mouth (PO), twice a day (BID), with up to 6 fixed doses Ad.p53 DC vaccinations every 2 weeks (q2wks). This phase 1 study used a 3+3 design with 7 indoximod dose levels (DL) (100 mg, 200 mg, 400 mg, 800 mg daily (QD) then 800 mg, 1,200 mg, and 1,600 mg PO BID +up to 6 fixed dose Ad.p53 DC vaccinations q2wks. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. The MTD is the highest dose level below the maximally administered dose (MAD) that is safely tolerated among 6 treated patients, that is, 0 or 1 out of 6 patients experiences a dose limiting toxicity (DLT).
Time Frame Up to 4 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Phase I Participants who Received at Least 1 Dose of Ad.p53DC+indoximod
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description:

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: indoximod dose in mg
1600
2.Primary Outcome
Title Phase 2 – Number of Participants With Stable Disease In Response to Study Therapy
Hide Description Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame Up to 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable participants at time of analysis
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description:

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: participants
4
3.Secondary Outcome
Title Phase 1 - Number of Participants With Objective Response at 6 Weeks
Hide Description Immunologic Response defined as Interferon-γ (IFN-γ) p53 T cell specific enzyme-linked immunospot (ELISPOT) assay count Summarized using both point estimates and the 95% exact confidence intervals based on the binomial distribution. Briefly, 2x10^5 mononuclear cells obtained from the peripheral blood of patients will be plated in quadruplicates in 96-well multiscreen mixed cellulose ester (HA) filtration plates, processed and incubated, spots will be visualized. The number of spots will be calculated per 10^6 cells. Untreated peripheral blood mononuclear cells (PBMNC) will represent a negative control and PBMNC stimulated with 10 µg/ml Concanavalin A (ConA) – positive control.
Time Frame At 6 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Phase I Participants who Received at Least 1 Dose of Ad.p53DC+indoximod
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description:

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
0
4.Secondary Outcome
Title Phase 2 – Number of Participants With Clinical Benefit From Chemotherapy After Vaccination
Hide Description Clinical response rate evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable participants at time of analysis
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description:

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 1
Partial Response (PR) 7
Stable Disease (SD) 2
5.Secondary Outcome
Title Phase 2 – Median Progression Free Survival (PFS) in Weeks
Hide Description Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS: Time from study entry to documentation of radiologic progressive disease or death, assessed up to 3 years.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable participants at time of analysis
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description:

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 21
Median (Full Range)
Unit of Measure: weeks
6.85
(3.8 to 18.1)
6.Other Pre-specified Outcome
Title Phase 2 - Change in Biomarker Level
Hide Description Biomarkers include serum kynurenine, serum tryptophan, C reactive protein, and circulating T-regulatory cell levels (CD4+ 25+ CD127low forkhead box protein 3+ (FoxP3+). Appropriate t-tests and/or Wilcoxon test will be employed to study changes over time.
Time Frame Baseline to week 16
Outcome Measure Data Not Reported
Time Frame 4 years, 3 months
Adverse Event Reporting Description Only 41 of 44 enrolled were at risk. 3 participants had disease progression prior to treatment.
 
Arm/Group Title Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Hide Arm/Group Description

Participants receive adenovirus-p53 transduced dendritic cell (Ad.p53-DC) vaccine ID in weeks 1, 3, 5, and 10, and then every 3 weeks for 6 total doses. Participants also receive 1-methyl-d-tryptophan (indoximod) orally (PO) daily (QD) on days 1-21. Treatment with 1-methyl-d-tryptophan repeats every 28 days (patients with stable disease) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

adenovirus-p53 transduced dendritic cell (DC) vaccine: Given intradermally (ID)

1-methyl-d-tryptophan: Given orally (PO)

Laboratory biomarker analysis: Correlative studies

All-Cause Mortality
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Affected / at Risk (%) # Events
Total   14/41 (34.15%)    
Blood and lymphatic system disorders   
Anemia  1  1/41 (2.44%)  2
Febrile neutropenia  1  1/41 (2.44%)  1
Eye disorders   
Eye disorders - Other, Visual disturbance  1  1/41 (2.44%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/41 (2.44%)  1
Constipation  1  1/41 (2.44%)  1
Nausea  1  1/41 (2.44%)  1
General disorders   
Fever  1  1/41 (2.44%)  1
Pain  1  1/41 (2.44%)  1
Infections and infestations   
Skin infection  1  2/41 (4.88%)  2
Investigations   
Alkaline phosphatase increased  1  1/41 (2.44%)  1
Aspartate aminotransferase increased  1  1/41 (2.44%)  1
Blood bilirubin increased  1  1/41 (2.44%)  1
Platelet count decreased  1  1/41 (2.44%)  1
Musculoskeletal and connective tissue disorders   
Bone pain  1  1/41 (2.44%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign - Other, Disease progression  1  2/41 (4.88%)  2
Nervous system disorders   
Nervous system disorder - Other, Disease progression  1  1/41 (2.44%)  1
Renal and urinary disorders   
Acute kidney injury  1  1/41 (2.44%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/41 (2.44%)  1
Respiratory failure  1  2/41 (4.88%)  2
Vascular disorders   
Hypotension  1  1/41 (2.44%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Affected / at Risk (%) # Events
Total   37/41 (90.24%)    
Blood and lymphatic system disorders   
Anemia  1  15/41 (36.59%)  32
Hemolysis  1  2/41 (4.88%)  2
Gastrointestinal disorders   
Nausea  1  15/41 (36.59%)  17
Constipation  1  9/41 (21.95%)  10
Vomiting  1  10/41 (24.39%)  13
Abdominal pain  1  8/41 (19.51%)  8
Diarrhea  1  7/41 (17.07%)  7
Dry mouth  1  2/41 (4.88%)  2
Dyspepsia  1  2/41 (4.88%)  2
Toothache  1  2/41 (4.88%)  2
General disorders   
Fatigue  1  27/41 (65.85%)  39
Edema limbs  1  5/41 (12.20%)  5
Fever  1  3/41 (7.32%)  4
Flu like symptoms  1  2/41 (4.88%)  2
Pain  1  2/41 (4.88%)  3
Infections and infestations   
Urinary tract infection  1  3/41 (7.32%)  3
Investigations   
Alkaline phosphatase increased  1  14/41 (34.15%)  20
Aspartate aminotransferase increased  1  12/41 (29.27%)  19
Lymphocyte count decreased  1  11/41 (26.83%)  16
Alanine aminotransferase increased  1  8/41 (19.51%)  11
White blood cell decreased  1  8/41 (19.51%)  10
Neutrophil count decreased  1  5/41 (12.20%)  5
Platelet count decreased  1  3/41 (7.32%)  5
Creatinine increased  1  2/41 (4.88%)  2
Metabolism and nutrition disorders   
Anorexia  1  14/41 (34.15%)  16
Hyperglycemia  1  13/41 (31.71%)  20
Hypoalbuminemia  1  10/41 (24.39%)  14
Hyponatremia  1  7/41 (17.07%)  9
Dehydration  1  4/41 (9.76%)  4
Hyperkalemia  1  3/41 (7.32%)  4
Hypocalcemia  1  3/41 (7.32%)  4
Hypokalemia  1  3/41 (7.32%)  4
Hypoglycemia  1  2/41 (4.88%)  2
Musculoskeletal and connective tissue disorders   
Back pain  1  7/41 (17.07%)  9
Bone pain  1  6/41 (14.63%)  8
Muscle weakness lower limb  1  4/41 (9.76%)  5
Chest wall pain  1  3/41 (7.32%)  3
Arthralgia  1  2/41 (4.88%)  2
Flank pain  1  2/41 (4.88%)  3
Nervous system disorders   
Headache  1  8/41 (19.51%)  8
Peripheral sensory neuropathy  1  7/41 (17.07%)  9
Reproductive system and breast disorders   
Breast pain  1  2/41 (4.88%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  10/41 (24.39%)  12
Cough  1  6/41 (14.63%)  7
Pleural effusion  1  2/41 (4.88%)  2
Skin and subcutaneous tissue disorders   
Alopecia  1  2/41 (4.88%)  2
Rash maculo-papular  1  2/41 (4.88%)  2
Vascular disorders   
Hypotension  1  2/41 (4.88%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Hatem Soliman, M.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-4933
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01042535     History of Changes
Other Study ID Numbers: NCI-8461
NCI-2013-00516 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MCC-16025 ( Other Identifier: H. Lee Moffitt Cancer Center and Research Institute )
P30CA076292 ( U.S. NIH Grant/Contract )
First Submitted: January 4, 2010
First Posted: January 5, 2010
Results First Submitted: February 19, 2015
Results First Posted: March 5, 2015
Last Update Posted: April 11, 2018