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)
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Castration-Resistant Prostate Carcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Number of Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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). 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.
Detailed Description
PRIMARY OBJECTIVE: 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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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.
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).
Arms & Interventions
Treatment (tremelimumab, durvalumab)
Patients 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.
Intervention: Durvalumab
Treatment (tremelimumab, durvalumab)
Patients 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.
Intervention: Tremelimumab
Outcomes
Primary Outcomes
Number of Adverse Events
Time Frame: 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.
Secondary Outcomes
- Radiographic Progressive Free Survival (rPFS)(from first day of treatment, up to 43.6 months)
- Number of Participants With PSA Decline of ≥50% From Start of Therapy(baseline, up to 43.6 months)
- Prostate-specific Antigen (PSA) Progression Free Survival (PFS)(from the first day of treatment, up to 43.6 months)
- Median Overall Survival(from start of treatment, up to 43.6 months)