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NCT01560923

Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer

Completed Phase 2 Results posted Last updated 3 April 2020
What this trial tests

Phase 2 trial testing Indoximod in Metastatic Prostate Cancer in 47 participants. Completed in 12 December 2018.

Timeline
1 October 2012
Primary endpoint
12 December 2018
12 December 2018

Quick facts

Lead sponsorMasonic Cancer Center, University of Minnesota
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment47
Start date1 October 2012
Primary completion12 December 2018
Estimated completion12 December 2018
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Masonic Cancer Center, University of Minnesota

Who can join

18 and older, male only, with Metastatic Prostate 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.

Immune Response to Sipuleucel-T Primary · 14 Weeks from First Leukapheresis

Assess the augmentation of immune response (PA2024) to sipuleucel-T measured at 14 weeks from first leukapheresis, in response to twice daily oral Indoximod at a dose of 1200 mg/day or an identical looking placebo. The frequency of antigen specific, cytokine producing cells will be determined by an ELISPOT assay. ELISPOT assay will use whole PBMC to assess interferon gamma production in response to the immunizing protein PA2024. Increase in number of ELISPOT responses to PBMC in patients in the treatment arm will be compared to those in control arm.

GroupValue95% CI
Sipuleucel-T + Placebo29.64.86 – 180.37
Sipuleucel-T + Oral Indoximod25.452.92 – 222.12
Number of Participants With Progression Free Survival at 6 Months Secondary · 6 Months

Progression free survival (PFS) is a composite endpoint defined as disease progression in bone or soft tissues, PSA progression, worsening pain, or death. PFS will be measured in months from the time of study enrollment until the date of disease progression. Progression is evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are

GroupValue95% CI
Sipuleucel-T + Placebo6
Sipuleucel-T + Oral Indoximod11
Objective Response Rate Secondary · 4 weeks

rate as defined by Prostate Cancer Working Group -2 (PCWG2). ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST)(version 1.1) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least

GroupValue95% CI
Sipuleucel-T + Placebo1
Sipuleucel-T + Oral Indoximod0
Sipuleucel-T + Placebo0
Sipuleucel-T + Oral Indoximod2
Sipuleucel-T + Placebo5
Sipuleucel-T + Oral Indoximod11
Sipuleucel-T + Placebo3
Sipuleucel-T + Oral Indoximod1
Overall Survival Secondary · 2 years

To evaluate 2 year overall survival

GroupValue95% CI
Sipuleucel-T + Placebo18
Sipuleucel-T + Oral Indoximod17
Quality of Life Scale Results Secondary · 6 Months

measured by the performance status with scale of 0-5 0 being 'normal activity' and 5 'being dead'

Baseline Performance Status Score
GroupValue95% CI
Sipuleucel-T + Placebo19
Sipuleucel-T + Oral Indoximod15
Sipuleucel-T + Placebo5
Sipuleucel-T + Oral Indoximod7
Sipuleucel-T + Placebo0
Sipuleucel-T + Oral Indoximod0
Post Treatment performance Status Score
GroupValue95% CI
Sipuleucel-T + Placebo7
Sipuleucel-T + Oral Indoximod9
Sipuleucel-T + Placebo10
Sipuleucel-T + Oral Indoximod3
Sipuleucel-T + Placebo7
Sipuleucel-T + Oral Indoximod10
Ratio of Antibodies to PA2024 Secondary · 14 Weeks from First Leukapheresis

Assess the augmentation of immune response (PA2024) to sipuleucel-T measured at 14 weeks from first leukapheresis, in response to twice daily oral Indoximod at a dose of 1200 mg/day or an identical looking placebo. The frequency of antigen specific, cytokine producing cells will be determined by an ELISPOT assay. ELISPOT assay will use whole PBMC to assess interferon gamma production in response to the immunizing protein PA2024. Antibodies to PA2024 is measured by ELISA. The ratio of antibodies to ELISPOT responses to PBMC in patients in the treatment arm will be compared to those in control

PA2024 IGG ratio (wk14/baseline)
GroupValue95% CI
Sipuleucel-T + Placebo13.055.05 – 33.72
Sipuleucel-T + Oral Indoximod9.193.04 – 27.8
PA2024 IGGIGM ratio (wk14/baseline)
GroupValue95% CI
Sipuleucel-T + Placebo104.3933.88 – 321.66
Sipuleucel-T + Oral Indoximod111.4335.49 – 349.89

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sipuleucel-T + Indoximod
Serious: 2/22 (9%)
Deaths: 5/22
Sipuleucel-T + Placebo
Serious: 1/24 (4%)
Deaths: 6/24

Serious adverse events (3 terms)

ReactionSystemSipuleucel-T + IndoximodSipuleucel-T + Placebo
Urinary tract obstructionRenal and urinary disorders
SepsisInfections and infestations
Flank painMusculoskeletal and connective tissue disorders
Other adverse events (108 terms — click to expand)

ReactionSystemSipuleucel-T + IndoximodSipuleucel-T + Placebo
FatiqueGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DiarrheaGastrointestinal disorders
PainGeneral disorders
Hot flashesVascular disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
ChillsGeneral disorders
FeverGeneral disorders
Flu like symptomsGeneral disorders
Bone painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Blurred visionEye disorders
BloatingGastrointestinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
GERDGastrointestinal disorders
Other general disorders -RefluxGeneral disorders
EdemaGeneral disorders
Upper respiratory infectionInfections and infestations
Weight gainInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
WeaknessMusculoskeletal and connective tissue disorders
Memory lossNervous system disorders
NueropathyNervous system disorders
ParesthesiaNervous system disorders
AnxietyPsychiatric disorders
Bladder incontinenceRenal and urinary disorders
Pelvic painReproductive system and breast disorders
Erectile DysfunctionReproductive system and breast disorders
CongestionRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Other; Slight rashSkin and subcutaneous tissue disorders
Positive ANA panel 1:320Blood and lymphatic system disorders

Most-reported serious reactions: Urinary tract obstruction, Sepsis, Flank pain.

Data from ClinicalTrials.gov NCT01560923 adverse events section.

Sponsor's own description

This is a randomized, double blind, multi-institutional phase II therapeutic study of Indoximod or placebo after the completion of standard of care sipuleucel-T (Provenge®) in men with asymptomatic or minimally symptomatic metastatic prostate cancer that is castration resistant (hormone refractory). Patients are randomized to receive either twice daily oral Indoximod or placebo for 6 months beginning the day after the third and final sipuleucel-T infusion.

Publications & conference data

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

  1. Inflammation and tumor progression: signaling pathways and targeted intervention.
    Zhao H, Wu L, Yan G, Chen Y, et al · · 2021 · cited 1932× · PMID 34248142 · DOI 10.1038/s41392-021-00658-5
  2. Next generation of immune checkpoint therapy in cancer: new developments and challenges.
    Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, et al · · 2018 · cited 582× · PMID 29544515 · DOI 10.1186/s13045-018-0582-8
  3. 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
  4. 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
  5. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy.
    Tang K, Wu YH, Song Y, Yu B. · · 2021 · cited 276× · PMID 33883013 · DOI 10.1186/s13045-021-01080-8
  6. 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
  7. 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
  8. 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

Verify or expand the search:

Other trials of Indoximod

Trials testing the same drug.

Other recruiting trials for Metastatic Prostate Cancer

Currently open trials in the same condition.

Other Masonic Cancer Center, University of Minnesota trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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