A Multi-centre Study to Assess the Safety, Tolerability, and Pharmacokinetics of Capivasertib (AZD5363) in Combination With Novel Agents in Patients With Metastatic Prostate Cancer

NCT04087174 | Completed Phase 1 FDA Drug

• 1 other identifier: D3618C00002
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a Phase Ib, open-label, multi-centre study to determine the safety, tolerability and pharmacokinetics (PK) of capivasertib when given in combination with novel agents (enzalutamide or abiraterone) to inform the selection of capivasertib dose regimens for each combination for further clinical evaluation when given to patients with metastatic castration resistant prostate cancer (CRPC). The study design allows an exploration of different doses with intensive safety monitoring to ensure the safety of the patients.

Conditions

Prostate Cancer

Keywords

Metastatic; Castration Resistant; Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Number of patients with dose limiting toxicity (DLT) for Part A1

  A DLT is defined as an AE that occurs from the first dose of study treatment up to and including the last day of the DLT period (day 1 to day 56 for Part A1) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications and that, despite optimal therapeutic interventions, meets any of the criteria defined in the protocol.

  Day 1 to day 56 for Part A1

• Number of patients with DLT for Part A2

  A DLT is defined as an AE that occurs from the first dose of study treatment up to and including the last day of the DLT period (day 1 to day 28 for Part A2) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications and that, despite optimal therapeutic interventions, meets any of the criteria defined in the protocol.

  Day 1 to day 28 for Part A2

• Number of patients with adverse events

  To investigate the safety and tolerability of capivasertib when given in combination with novel agents (enzalutamide and abiraterone) to patients with metastatic CRPC.

  For each treatment combination, from screening (Day -28 to -1) either for up to 1.5 years or up to 30 days follow-up period after discontinuation

Secondary Outcomes (6)

• Area under curve (AUC) for capivasertib to characterize pharmacokinetics (PK) for each treatment combination

  For capivasertib and enzalutamide combination, full sampling on day 25 and on day 53; for capivasertib and abiraterone combination, full sampling on day 25.

• Maximum plasma concentration (Cmax) for capivasertib to characterize PK for each treatment combination

  For capivasertib and enzalutamide combination, full sampling on day 25 and on day 53; for capivasertib and abiraterone combination, full sampling on day 25.

• Soft tissue objective response rate (ORR) and radiological ORR for efficacy analyses of capivasertib for each treatment combination

  From screening (-28 Day) to every 8 weeks after cycle 1 day 1 for the first 24 weeks and every 12 weeks thereafter up to 1.5 years for each treatment combination

• Duration of response (DoR) for efficacy analyses of capivasertib for each treatment combination

  From screening (-28 Day) to every 8 weeks after cycle 1 day 1 for the first 24 weeks and every 12 weeks thereafter up to 1.5 years for each treatment combination

• Percentage change in tumour size for efficacy analyses of capivasertib for each treatment combination

  From screening (-28 Day) to every 8 weeks after cycle 1 day 1 for the first 24 weeks and every 12 weeks thereafter up to 1.5 years for each treatment combination

Study Arms (6)

Part A1: Capivasertib + enzalutamide

EXPERIMENTAL

From day 1 to day 28 of this study treatment, patients will continuously enroll on a starting dose of capivasertib in combination with 160 mg enzalutamide.

Drug: Capivasertib; Drug: Enzalutamide

Part A1: Capivasertib dose level 1 + enzalutamide

EXPERIMENTAL

On day 29 of the treatment, patients will escalate the capivasertib dose to dose level+1 along with 160 mg enzalutamide.

Drug: Capivasertib; Drug: Enzalutamide

Part A1: Capivasertib dose level 2 + enzalutamide

EXPERIMENTAL

On day 29 of the treatment, patients will escalate the capivasertib dose to dose level+2 along with 160 mg enzalutamide.

Drug: Capivasertib; Drug: Enzalutamide

Part A2: Capivasertib + abiraterone

EXPERIMENTAL

Patients will continuously enroll on a starting dose of capivasertib in combination with 1000 mg abiraterone.

Drug: Capivasertib; Drug: Abiraterone

Part B1: Capivasertib + enzalutamide

EXPERIMENTAL

This optional expansion will treat patients at the recommended dose regimen of capivasertib and enzalutamide.

Drug: Capivasertib; Drug: Enzalutamide

Part B2: Capivasertib + abiraterone

EXPERIMENTAL

This optional expansion will treat patients at the recommended dose regimen of capivasertib and abiraterone.

Drug: Capivasertib; Drug: Abiraterone

Interventions

Capivasertib DRUG

Patients will receive multiple oral dose of capivasertib.

Also known as: AZD5363

Part A1: Capivasertib + enzalutamide; Part A1: Capivasertib dose level 1 + enzalutamide; Part A1: Capivasertib dose level 2 + enzalutamide; Part A2: Capivasertib + abiraterone; Part B1: Capivasertib + enzalutamide; Part B2: Capivasertib + abiraterone

Enzalutamide DRUG

Patients will receive 160 mg oral dose of enzalutamide.

Part A1: Capivasertib + enzalutamide; Part A1: Capivasertib dose level 1 + enzalutamide; Part A1: Capivasertib dose level 2 + enzalutamide; Part B1: Capivasertib + enzalutamide

Abiraterone DRUG

Patients will receive 1000 mg oral dose of abiraterone.

Part A2: Capivasertib + abiraterone; Part B2: Capivasertib + abiraterone

Eligibility Criteria

• Age: 18 Years - 130 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol prior to any mandatory study-specific procedures, sampling, and analyses.
• Males aged 18 years and older at the time of signing the ICF.
• Patients with documented evidence of metastatic CRPC who have had at least one line of systemic therapy for metastatic CRPC (either chemotherapy or an novel hormonal agents \[NHA\]) or for whom no alternative approved therapy is available.
• World Health Organization (WHO) performance status 0 to 2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks, as assessed at day 1.
• Patients must be able to swallow and retain oral medication.
• Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
• Sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
• Patients should use barrier contraception (ie, condoms) from the time of screening until 16 weeks after discontinuation of study treatment. It is not known whether the preclinical changes seen in the male animal reproductive organs, after treatment with capivasertib, will be fully reversible or will permanently affect the ability to produce healthy sperm following treatment. Therefore, if patients wish to father children they should be advised to arrange for collection of sperm samples prior to the start of study treatment.

You may not qualify if:

• Previous enrolment in the present study.
• Prior enzalutamide therapy in the last 8 weeks.
• Treatment with any of the following:
• Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment.
• Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment.
• Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anti-cancer agents within 3 weeks of the first dose of study treatment, except hormonal therapy with luteinising hormone-releasing hormone (LHRH) analogues for medical castration in patients with prostate cancer, which are permitted.
• Potent inhibitors or inducers or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St. John's wort) or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to the first dose of study treatment.
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
• Radiotherapy with a wide field of radiation within 4 weeks of the first dose of study treatment.
• Clinically significant abnormalities of glucose metabolism as defined by any of the following:
• Diabetes mellitus Type I or Type II requiring insulin treatment.
• HbA1c ≥8.0% (63.9 mmol/mol).
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (6)

Research Site

Indianapolis, Indiana, 46202, United States

Location

Research Site

Omaha, Nebraska, 68114, United States

Location

Research Site

White Plains, New York, 10601, United States

Location

Research Site

Gettysburg, Pennsylvania, 17325, United States

Location

Research Site

Myrtle Beach, South Carolina, 29572, United States

Location

Research Site

Barcelona, 08036, Spain

Location

Related Publications (1)

• Shore N, Mellado B, Shah S, Hauke R, Costin D, Adra N, Cullberg M, Teruel CF, Morris T. A Phase I Study of Capivasertib in Combination With Abiraterone Acetate in Patients With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer. 2023 Apr;21(2):278-285. doi: 10.1016/j.clgc.2022.11.017. Epub 2022 Nov 26.

  PMID: 36572571 DERIVED

Related Links

• CSR Synopsis
• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

capivasertib; enzalutamide; abiraterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will include up to approximately 87 evaluable patients, divided among the 4 study parts.

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: September 12, 2019
• Study Start: August 5, 2019
• Primary Completion: June 22, 2021
• Study Completion: June 22, 2021
• Last Updated: July 13, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

ES (1); US (5)