Open Label Prostate Cancer Study

NCT01162395 | Completed Phase 1

• 3 other identifiers: D3760C000012010-020232-19IND 111707
• Study Type: interventional
• Target: 64
• Locations: 3 countries
• Sites: 5

Brief Summary

The main purpose of the study is to investigate the safety and tolerability of AZD3514 when given orally to patients with castration-resistant prostate cancer (CRPC)

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Tumour; Castration Resistant; Prostate Androgen Receptor Down Regulator; Metastatic

Outcome Measures

Primary Outcomes (1)

• To investigate the safety and tolerability of AZD3514 when given orally to patients with CRPC.

  At every visit.

Secondary Outcomes (8)

• To define the MTD, if possible, a lower biologically-effective dose(s) or maximum feasible dose (if decided by the Safety Review Committee (SRC) and AstraZeneca).

  After each Cohort.

• To characterise the PK of AZD3514 after a single oral dose and at steady state after multiple oral doses.

  After each Cohort.

• To obtain an assessment of the activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate on the circulating levels of prostate-specific antigen (PSA).

  Visits 1, 4, 6, 7, 9, 10, follow-up visits, discontinuation visit

• To obtain a preliminary assessment of the anti-tumour activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate by evaluation of counts of Circulating Tumour Cells (CTCs).

  Visits 1, 6, 8, 9, 10, follow-up visits, discontinuation visit

• To obtain an assessment of the activity of AZD3514 as monotherapy and/or in combination with abiraterone acetate on the circulating levels of prostate-specific antigen (PSA).

  Visits 1, 10, follow-up visits, discontinuation visit

Study Arms (1)

A

EXPERIMENTAL

Ascending doses of AZD3514 administered orally to patients to define the maximum tolerated dose (MTD)

Drug: AZD3514

Interventions

AZD3514 DRUG

Patients will be given AZD3514 orally as a single dose, and then multiple once daily dosing following a 5-9 day washout.

A

Eligibility Criteria

• Age: 20 Years - 130 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged 20 years or older.
• Histologically or Cytologically proven diagnosis of prostate cancer for which no standard therapy is currently considered appropriate.
• Documented evidence of metastatic prostate cancer
• Presence of progressive disease defined as one or more:
• Biochemical progression of the prostate cancer
• Progression as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 guidelines
• Two or more new metastatic bone lesions from bone scans from a previous assessment
• Serum testosterone concentration less or equals 50 ng/dL
• World Health Organization (WHO) performance status 0 to 1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
• Sexually active males should be willing to use condoms
• Have received prior chemotherapy containing or based on docetaxel
• Not have received prior treatment with abiraterone acetate, MDV3100, TAK700, TOK001 or other similar therapies which target the AR axis or with selective AR down-regulator-like properties
• Have been stable on abiraterone acetate abiraterone acetate for ≥ 4 months (i.e. stable PSA values) and have achieved ≥ 50% reduction in PSA while being treated with abiraterone acetate
• Provide informed consent for paired tumour biopsy sampling
• Have bone or soft tissue lesions that are suitable for paired biopsy sampling

You may not qualify if:

• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAEv4) grade 1 except for alopecia or toxicities related to the use of gonadotropin-releasing hormone agonists
• Medically important spinal cord compression or brain metastases
• Medically important evidence of severe or uncontrolled systemic disease
• History of hypersensitivity to active or inactive excipients of AZD3514 or drugs with a similar chemical structure or class to AZD3514
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD3514
• Inadequate bone marrow reserve or organ function
• Any medically important factors identified from electrocardiogram (ECG) measurements
• Concurrent or recent treatment with certain medications or medical procedures
• The following criteria exclude patients from entering the AZD3514 administered in combination with abiraterone acetate cohort(s):
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases or conditions, including adrenocortical insufficiency or a history of cardiovascular disease including heart failure (currently there are no randomized data for the use of abiraterone acetate in patients with LVEF \< 50% or NYHA Class III or IV heart failure), which would make it undesirable for the patient to participate in the trial. See the full local prescribing information for abiraterone acetate for more detail
• Child-Pugh class B and C hepatic impairment
• If unable to fast for ≥ 2 hours prior to taking a dose to ≥ 1 hour post dose
• Received abiraterone acetate treatment previously
• Known hypersensitivity to components of prednisone or prednisolone
• Any systemic fungal infections

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Portland, Oregon, United States

Location

Research Site

Amsterdam, Netherlands

Location

Research Site

Glasgow, United Kingdom

Location

Research Site

Manchester, United Kingdom

Location

Research Site

Surrey, United Kingdom

Location

Related Publications (1)

• James GD, Symeonides SN, Marshall J, Young J, Clack G. Continual reassessment method for dose escalation clinical trials in oncology: a comparison of prior skeleton approaches using AZD3514 data. BMC Cancer. 2016 Aug 31;16(1):703. doi: 10.1186/s12885-016-2702-6.

  PMID: 27581751 DERIVED

Related Links

• D3760C00001 Clinical Report Synopsis

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

AZD3514

Condition Hierarchy (Ancestors)

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

Study Officials

• Tony Elliott, MD

  The Christie Hospital

  PRINCIPAL INVESTIGATOR

• Glen Clack, MD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 14, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: October 1, 2015
• Last Updated: January 12, 2016

Record last verified: 2016-01

Locations

GB (3); US (1); NL (1)