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Castration-Resistant Prostate CarcinomaPhase 2NCT03204812

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

A Phase 2 study testing Durvalumab and Tremelimumab in people with Castration-Resistant Prostate Carcinoma and Metastatic Malignant Neoplasm in the Bone, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
14 Jul 2017to 13 Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy of >= 52 weeks.
  • Hemoglobin >= 11.0 g/dL.
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3).
  • Platelet count >= 100 x 10^9/L (>100,000 per mm^3).
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  • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase [ALT] serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal.
  • Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Consent to MD Anderson laboratory protocol PA13-0291 and LAB02-152.
  • Willing to have peripheral blood mononuclear cells and bone marrow biopsies to be collected prior to receiving the first dose of durvalumab and tremelimumab, after 2-doses and 4-doses of durvalumab and tremelimumab, after 2nd treatment administration and 4th treatment administration.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate.
  • Evidence of metastatic disease to the bone seen on most recent bone scan, computed tomography (CT) scan and/or magnetic resonance imaging (MRI).
  • Asymptomatic or minimally symptomatic patients (do not require narcotics for prostate cancer-related pain).
  • Tumor progression while on hormone therapy with castrate levels serum testosterone (=< 1.7 nmol/L or 50 ng/dL) defined by prostate-specific antigen (PSA) and/or radiographic criteria according to the Prostate Cancer Working Group 3 (PCWG3). Castrate levels of testosterone must be maintained by surgical or medical means throughout the conduct of the study.

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site), previous enrollment in the present study.
  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
  • History of another primary malignancy except for: 1) Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence. 2) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3) Adequately treated carcinoma in situ without evidence of disease (e.g., superficial bladder cancer).
  • Evidence of visceral metastasis to the liver.
  • Prior use of taxane-based chemotherapy for treatment of castrate resistant prostate cancer.
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  • Receipt of the last dose of anti-cancer therapy (immunotherapy, endocrine therapy [e.g., abiraterone acetate, enzalutamide], targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug. (with the exception of any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.)
  • Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of durvalumab or tremelimumab. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms. Any clinically significant abnormalities detected, require triplicate electrocardiogram (ECG) results and a mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms calculated from 3 electrocardiograms (ECGs).
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of: intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid or steroids as pre-medication for hypersensitivity reactions (e.g. CT scan premedication).
  • Any unresolved toxicity (Common Terminology Criteria for Adverse Events [CTCAE] grade >= 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia;
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
  • Any chronic skin condition that does not require systemic therapy;
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician;
  • Patients with celiac disease controlled by diet alone.
  • Subjects with history of diverticulitis may be included only after consultation and approval of the study physician.
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • History of hypersensitivity to the combination of durvalumab and tremelimumab.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Known history of positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
  • History of leptomeningeal carcinomatosis.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  • Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 28 days prior to study treatment start. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.
  • Subjects with uncontrolled seizures.
  • Male patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
  • A malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years, or has a >= 30% probability of recurrence within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Pilot Trial to Explore the Link Between Immunological Changes, Efficacy, Safety, and Tolerability of Durvalumab (MEDI4736) Plus Tremelimumab in Chemotherapy-Naïve Men With Metastatic Castration-Resistant Prostate Cancer (CRPC)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of durvalumab plus tremelimumab in patients with metastatic castration-resistant prostate cancer.

SECONDARY OBJECTIVES:

  1. To assess the efficacy of durvalumab plus tremelimumab in patients with metastatic castration-resistant prostate cancer. II. To explore immunological changes in peripheral blood and tissue (e.g. peripheral blood cluster of differentiation [CD] 4+ [Inducible COStimulator (ICOS)]+ T cells, CD3 expression in tissue) in response to durvalumab plus tremelimumab in patients with metastatic castration-resistant prostate cancer.

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 60 minutes and durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles for tremelimumab and up to 13 cycles for durvalumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then every 3 months thereafter.

Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • TremelimumabBiological

    Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206

    Given IV

Study groups in NCT03204812
Study groupRoleWhat they receive
Treatment (tremelimumab, durvalumab)ExperimentalPatients receive tremelimumab IV over 60 minutes and durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles for tremelimumab and up to 13 cycles for durvalumab in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Durvalumab; Biological: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Adverse Events

    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.

    Measured: from date of the first treatment, up to 43.6 months

Secondary outcomes (4)

  1. Prostate-specific Antigen (PSA) Progression Free Survival (PFS)

    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.

    Measured: from the first day of treatment, up to 43.6 months

  2. Radiographic Progressive Free Survival (rPFS)

    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

    Measured: from first day of treatment, up to 43.6 months

  3. Number of Participants With PSA Decline of ≥50% From Start of Therapy

    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.

    Measured: baseline, up to 43.6 months

  4. Median Overall Survival

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

    Measured: from start of treatment, up to 43.6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2017
  2. Study start14 Jul 2017
  3. Primary completion13 Apr 2021
  4. Study completion13 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03204812
Sponsor's protocol ID
2016-0769
Other IDs
NCI-2018-01135, 2016-0769
Status last verified
Oct 2023
First submitted
28 Jun 2017
Last updated
15 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Subudhi SK, Siddiqui BA, Aparicio AM, Yadav SS, Basu S, Chen H, Jindal S, Tidwell RSS, Varma A, Logothetis CJ, Allison JP, Corn PG, Sharma P. Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naive metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment. J Immunother Cancer. 2021 Oct;9(10):e002919. doi: 10.1136/jitc-2021-002919.

    PubMed 34663638

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Tremelimumab in people with Castration-Resistant Prostate Carcinoma and Metastatic Malignant Neoplasm in the Bone, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events (time frame: from date of the first treatment, up to 43.6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03204812, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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