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NCT01042535

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

Completed Phase 1, PHASE2 Results posted Last updated 11 April 2018
What this trial tests

Phase 1, PHASE2 trial testing adenovirus-p53 transduced dendritic cell (DC) vaccine in Male Breast Cancer in 44 participants. Completed in 27 February 2018.

Timeline
28 December 2009
Primary endpoint
1 December 2014
27 February 2018

Quick facts

Lead sponsorH. Lee Moffitt Cancer Center and Research Institute
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment44
Start date28 December 2009
Primary completion1 December 2014
Estimated completion27 February 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Who can join

18 and older, any sex, with Male Breast Cancer or Recurrent Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1 - Maximum Tolerated Dose (MTD) in Milligrams (mg) Primary · Up to 4 weeks

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

GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)1600
Phase 2 - Number of Participants With Stable Disease In Response to Study Therapy Primary · Up to 16 weeks

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.

GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)4
Phase 1 - Number of Participants With Objective Response at 6 Weeks Secondary · At 6 weeks

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 negati

GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)0
Phase 2 - Number of Participants With Clinical Benefit From Chemotherapy After Vaccination Secondary · Up to 3 years

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.

Complete Response (CR)
GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)1
Partial Response (PR)
GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)7
Stable Disease (SD)
GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)2
Phase 2 - Median Progression Free Survival (PFS) in Weeks Secondary · Up to 3 years

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.

GroupValue95% CI
Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)6.853.8 – 18.1

Adverse events — posted to ClinicalTrials.gov

Time frame: 4 years, 3 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Vaccine Therapy, 1-methyl-d-tryptophan)
Serious: 14/41 (34%)
Deaths:

Serious adverse events (20 terms)

ReactionSystemTreatment (Vaccine Therapy…
Skin infectionInfections and infestations
Neoplasms benign - Other, Disease progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Respiratory failureRespiratory, thoracic and mediastinal disorders
AnemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Eye disorders - Other, Visual disturbanceEye disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
FeverGeneral disorders
PainGeneral disorders
Alkaline phosphatase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Platelet count decreasedInvestigations
Bone painMusculoskeletal and connective tissue disorders
Nervous system disorder - Other, Disease progressionNervous system disorders
Acute kidney injuryRenal and urinary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Other adverse events (48 terms — click to expand)

ReactionSystemTreatment (Vaccine Therapy…
FatigueGeneral disorders
NauseaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
White blood cell decreasedInvestigations
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
HyponatremiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Peripheral sensory neuropathyNervous system disorders
Bone painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
Neutrophil count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
Muscle weakness lower limbMusculoskeletal and connective tissue disorders
FeverGeneral disorders
HyperkalemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
Platelet count decreasedInvestigations
Chest wall painMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
Flu like symptomsGeneral disorders
PainGeneral disorders
HypoglycemiaMetabolism and nutrition disorders
Creatinine increasedInvestigations
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
ToothacheGastrointestinal disorders

Most-reported serious reactions: Skin infection, Neoplasms benign - Other, Disease progression, Respiratory failure, Anemia, Febrile neutropenia, Eye disorders - Other, Visual disturbance, Abdominal pain, Constipation.

Data from ClinicalTrials.gov NCT01042535 adverse events section.

Sponsor's own description

This randomized phase I/II trial studies the side effects and best dose of vaccine therapy and to see how well it works when given together with 1-methyl-D-tryptophan (1-MT) in treating patients with metastatic breast cancer. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting the IDO1 pathway in cancer: from bench to bedside.
    Liu M, Wang X, Wang L, Ma X, et al · · 2018 · cited 339× · PMID 30068361 · DOI 10.1186/s13045-018-0644-y
  2. IDO1 in cancer: a Gemini of immune checkpoints.
    Zhai L, Ladomersky E, Lenzen A, Nguyen B, et al · · 2018 · cited 319× · PMID 29375124 · DOI 10.1038/cmi.2017.143
  3. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy.
    Patente TA, Pinho MP, Oliveira AA, Evangelista GCM, et al · · 2018 · cited 295× · PMID 30719026 · DOI 10.3389/fimmu.2018.03176
  4. Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy.
    Zhai L, Spranger S, Binder DC, Gritsina G, et al · · 2015 · cited 262× · PMID 26519060 · DOI 10.1158/1078-0432.ccr-15-0420
  5. Targeting the indoleamine 2,3-dioxygenase pathway in cancer.
    Moon YW, Hajjar J, Hwu P, Naing A. · · 2015 · cited 255× · PMID 26674411 · DOI 10.1186/s40425-015-0094-9
  6. Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.
    Xie X, Yu T, Li X, Zhang N, et al · · 2023 · cited 246× · PMID 37669923 · DOI 10.1038/s41392-023-01589-z
  7. Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment.
    Saxena M, Bhardwaj N. · · 2018 · cited 231× · PMID 29458962 · DOI 10.1016/j.trecan.2017.12.007
  8. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?
    Colbeck EJ, Ager A, Gallimore A, Jones GW. · · 2017 · cited 198× · PMID 29312327 · DOI 10.3389/fimmu.2017.01830

Verify or expand the search:

Other recruiting trials for Male Breast Cancer

Currently open trials in the same condition.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing