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

NCT03204812 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0769NCI-2018-01135
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Malignant Neoplasm in the Bone; Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (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.

  from date of the first treatment, up to 43.6 months

Secondary Outcomes (4)

• Prostate-specific Antigen (PSA) Progression Free Survival (PFS)

  from the first day of treatment, up to 43.6 months

• 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

• Median Overall Survival

  from start of treatment, up to 43.6 months

Study Arms (1)

Treatment (tremelimumab, durvalumab)

EXPERIMENTAL

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.

Biological: Durvalumab; Biological: Tremelimumab

Interventions

Durvalumab BIOLOGICAL

Given IV

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

Treatment (tremelimumab, durvalumab)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Treatment (tremelimumab, durvalumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:
• 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;

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34663638 DERIVED

Related Links

• The University of Texas (UT) MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

durvalumab; Immunoglobulin G; Disulfides; tremelimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Sumit Subudhi, PhD-Associate Professor, Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

sksubudhi@mdanderson.org

(713) 792-2830

Study Officials

• Sumit K Subudhi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 2, 2017
• Study Start: July 14, 2017
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: October 15, 2024
• Results First Posted: May 25, 2022

Record last verified: 2023-10

Locations

US (1)