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NCT03204812

Durvalumab and Tremelimumab in Treating Chemotherapy Naive Patients With Metastatic Castration-Resistant Prostate Cancer

Completed Phase 2 Results posted Last updated 15 October 2024
What this trial tests

Phase 2 trial testing Durvalumab in Castration-Resistant Prostate Carcinoma in 31 participants. Completed in 13 April 2021.

Timeline
14 July 2017
Primary endpoint
13 April 2021
13 April 2021

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment31
Start date14 July 2017
Primary completion13 April 2021
Estimated completion13 April 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Castration-Resistant Prostate Carcinoma or Metastatic Malignant Neoplasm in the Bone. 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.

Number of Adverse Events Primary · from date of the first treatment, up to 43.6 months

Toxicity will be monitored in all patients who receive at least one dose of tremelimumab, even if the patient is not evaluable for the biomarker or efficacy endpoint. Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03.

Adverse Events
GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)236
Serious Adverse Events
GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)14
Prostate-specific Antigen (PSA) Progression Free Survival (PFS) Secondary · from the first day of treatment, up to 43.6 months

PSA PFS is defined as per Prostate Cancer Working Group 3 (PCWG3) criteria: time from start of therapy to first PSA increase of 25% and ≥2 ng/mL above the nadir, and which is confirmed by a second value ≥3 weeks later. PSA PFS were calculated from the first day of treatment and summarized by Kaplan-Meier methods.

GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)0.90.9 – 1.8
Radiographic Progressive Free Survival (rPFS) Secondary · from first day of treatment, up to 43.6 months

rPFS is measured from first dose to date of disease progression on CT and/or bone scan or death from any cause, whichever occurs first. Radiographic PFS will start at the first day of treatment and will be summarized by Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1),as a 20% increase in the sum of the longest diameter of target lesions, or ameasurable increase in a non-target lesion, or the appearance of new lesions

GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)3.71.9 – 5.7
Number of Participants With PSA Decline of ≥50% From Start of Therapy Secondary · baseline, up to 43.6 months

PSA decline will start at the first day of treatment and will be summarized by Kaplan-Meier. The numeric PSA value at maximal decline will be summarized by a boxplot and as a scatter plot of maximal decline by baseline PSA. PSA is produced by normal and cancerous prostate tissue. PSA levels are often elevated in men with prostate cancer.

GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)3
Median Overall Survival Secondary · from start of treatment, up to 43.6 months

Overall Survival is the time which begins at diagnosis (or at the start of treatment) and up to the time of death.

GroupValue95% CI
Treatment (Tremelimumab, Durvalumab)28.114.5 – 37.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose through 30 days after the last dose of medication, up to 43.6 months. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Tremelimumab, Durvalumab)
Serious: 10/26 (38%)
Deaths: 14/26

Serious adverse events (11 terms)

ReactionSystemTreatment (Tremelimumab, D…
ColitisGastrointestinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Diabetes type 1Endocrine disorders
EnterocolitisGastrointestinal disorders
Lipase increasedBlood and lymphatic system disorders
Lung infectionInfections and infestations
Spinal Cord CompressionMusculoskeletal and connective tissue disorders
MyositisMusculoskeletal and connective tissue disorders
PainGeneral disorders
Peripheral sensory neuropathyNervous system disorders
Urinary tract infectionInfections and infestations
Other adverse events (74 terms — click to expand)

ReactionSystemTreatment (Tremelimumab, D…
AnemiaBlood and lymphatic system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
FatigueGeneral disorders
Aspartate aminotransferase increasedInvestigations
Lipase increasedInvestigations
Serum amylase increasedInvestigations
Alanine aminotransferase increasedInvestigations
AnorexiaMetabolism and nutrition disorders
Increased cortisolEndocrine disorders
HypothyroidismEndocrine disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased cortisolEndocrine disorders
Increased sedimentation rateInvestigations
Creatinine increasedInvestigations
Dry skinSkin and subcutaneous tissue disorders
HypoalbuminemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
ColitisGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypophysitisEndocrine disorders
Decreased ACTHEndocrine disorders
Increased non-fasting blood glucoseEndocrine disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
GGT increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypernatremiaMetabolism and nutrition disorders
HyperthyroidismEndocrine disorders
MyalgiaMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
White blood cell decreasedInvestigations
Alkaline phosphatase increasedInvestigations
Atrial fibrillationCardiac disorders
BloatingGastrointestinal disorders
Blurred visionEye disorders
Cardiac troponin I increasedInvestigations

Most-reported serious reactions: Colitis, Pneumonitis, Diabetes type 1, Enterocolitis, Lipase increased, Lung infection, Spinal Cord Compression, Myositis.

Data from ClinicalTrials.gov NCT03204812 adverse events section.

Sponsor's own description

This phase II trial studies the safety, tolerability and how well durvalumab and tremelimumab work in treating participants with castration-resistant prostate cancer who have not received chemotherapy (chemotherapy naïve) and has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Publications & conference data

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

  1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  2. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.
    He Y, Xu W, Xiao YT, Huang H, et al · · 2022 · cited 192× · PMID 35750683 · DOI 10.1038/s41392-022-01042-7
  3. How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
    Stultz J, Fong L. · · 2021 · cited 173× · PMID 33820953 · DOI 10.1038/s41391-021-00340-5
  4. Novel therapies are changing treatment paradigms in metastatic prostate cancer.
    Powers E, Karachaliou GS, Kao C, Harrison MR, et al · · 2020 · cited 89× · PMID 33115529 · DOI 10.1186/s13045-020-00978-z
  5. PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.
    Isaacsson Velho P, Antonarakis ES. · · 2018 · cited 82× · PMID 29641940 · DOI 10.1080/17512433.2018.1464388
  6. Is There a Role for Immunotherapy in Prostate Cancer?
    Rizzo A, Mollica V, Cimadamore A, Santoni M, et al · · 2020 · cited 68× · PMID 32911806 · DOI 10.3390/cells9092051
  7. Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment.
    Subudhi SK, Siddiqui BA, Aparicio AM, Yadav SS, et al · · 2021 · cited 44× · PMID 34663638 · DOI 10.1136/jitc-2021-002919
  8. Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives.
    Taghizadeh H, Marhold M, Tomasich E, Udovica S, et al · · 2019 · cited 25× · PMID 31646092 · DOI 10.1080/2162402x.2019.1644109

Verify or expand the search:

Other trials of Durvalumab

Trials testing the same drug.

Other recruiting trials for Castration-Resistant Prostate Carcinoma

Currently open trials in the same condition.

Other M.D. Anderson Cancer Center trials

Trials by the same sponsor.

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