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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03204812
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : January 2, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the safety, tolerability and how well durvalumab and tremelimumab work in treating participants with metastatic castration-resistant prostate cancer who have not received chemotherapy. 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.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Prostate Adenocarcinoma Prostate Carcinoma Metastatic in the Bone Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8 Biological: Durvalumab Biological: Tremelimumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. 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 8 hours and durvalumab IV over 8 hours 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 14, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Treatment (tremelimumab, durvalumab)
Patients receive tremelimumab IV over 8 hours and durvalumab IV over 8 hours 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.
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736

Biological: Tremelimumab
Given IV
Other Names:
  • Anti-CTLA4 Human Monoclonal Antibody CP-675,206
  • CP-675
  • CP-675,206
  • CP-675206
  • Ticilimumab




Primary Outcome Measures :
  1. Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. Prostate-specific antigen (PSA) progression-free survival [ Time Frame: Up to 12 months ]
    The association between CD3 change and PSA PFS will be explored with a Cox model with CD3 as a continuous measure.

  2. Radiographic PFS [ Time Frame: Up to 12 months ]
    Radiographic PFS will start at the first day of treatment and will be summarized by Kaplan-Meier.

  3. Time to maximal PSA decline [ Time Frame: Up to 12 months ]
    Time to maximal 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.

  4. Immunological changes in peripheral blood and tissue [ Time Frame: Baseline up to 12 months ]
    For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum or interquartile range (IQR) will be computed. Prostatic T cell infiltration pre-and-post biopsy will be described and graphed over time. Differences in either time point compared to baseline will be compared with a t-test or non-parametric alternative. Cox models will be implemented to explore the relationship of treatment combination, prostatic T cell infiltration, and PFS.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).
  • 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.

Exclusion Criteria:

  • 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.
  • 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: 1) Patients with vitiligo or alopecia; 2) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; 3) Any chronic skin condition that does not require systemic therapy; 4) Patients without active disease in the last 5 years may be included but only after consultation with the study physician; 5) 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03204812


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sumit K Subudhi M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03204812    
Other Study ID Numbers: 2016-0769
NCI-2018-01135 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0769 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Durvalumab
Ipilimumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs