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Phase I Open Label Dose Escalation Study to Investigate the Safety & Pharmacokinetics of AZD5312 in Patients With Androgen Receptor Tumors | Clinical Trials | Clareo Health

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Phase I Open Label Dose Escalation Study to Investigate the Safety & Pharmacokinetics of AZD5312 in Patients With Androgen Receptor Tumors

A Phase I, Open-Label, Multicentre Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD5312 in Patients With Advanced Solid Tumours Where the Androgen Receptor Pathway is a Potential Factor

NCT02144051•AstraZeneca

View on ClinicalTrials.gov

Summary

This is a first time in man (FTIM), Phase I study to determine the Maximum Tolerated Dose, Recommended Phase 2 Dose, safety, tolerability and Pharmacokinetics of AZD5312. This is a multicentre study with sites in the United States and United Kingdom. Approximately 90 patients are expected to be enrolled in this study. The study involves two parts, Part A, Dose Escalation and Part B, Dose Expansion.

Detailed Description

This is a first time in man (FTIM), Phase I study to determine the Maxiimum Tolerated Dose, Recommended Phase 2 Dose, safety, tolerability and Pharmacokinetics of AZD5312. This is a multicentre study with sites in the United States and United Kingdom. Approximately 90 patients are expected to be enrolled in this study.The study involves two parts, Part A, Dose Escalation and Part B, Dose Expansion. AZD5312 will be given intravenously (IV) as an infusion, over one hour. For the purpose of planning, each 4 week period (28 days) will be called a Cycle. AZD5312 will initially be administered 4 times within the first 11 days, (on Days \[1, 4, 8 and 11\]± 2), with no dosing on sequential days. Patients will receive weekly treatments on Days 15 and 22 to complete Cycle. 1\. During the subsequent cycles, patients will receive weekly treatment on Days 1, 8, 15 and 22 (±2). The AZD5312 dose will not change unless dose reductions are required due to treatment-related toxicity. Patients will continue to receive AZD5312 until disease progression, intolerable toxicity, or discontinuation criteria have been met. Toxicity, Pharmacokinetics and biomarker data will be assessed throughout the study. Alternative infusion durations and/or treatment schedules may be explored if preliminary data suggest these would be more appropriate.

Eligibility

Age

18 - 130 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patient must understand nature of trial and provide a signed and dated, written informed consent form prior to study specific procedures, sampling and analyses. If a patient declines to participate in voluntary exploratory research and/or genetic component of study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study.
•Part A Dose Escalation Patients must have histological or cytological confirmation of a solid tumour of either locally advanced or metastatic castrate resistant prostate cancer (mCRPC), breast, bladder, ovarian, gastric or salivary duct carcinoma where an Androgen Receptor pathway may be a potential factor.
•Part B Dose Expansion.
•* Patient must understand nature of trial and provide a signed and dated, written informed consent form prior to any study specific procedures, sampling and analyses.
•* Part A Dose Escalation Patients must have histological or cytological confirmation of a solid tumour of either locally advanced or metastatic castrate resistant prostate cancer (mCRPC), breast, bladder, ovarian, gastric or salivary duct carcinoma where an Androgen Receptor pathway may be a potential factor.
•* Part B Dose Expansion Arm 1 and 2 patients must have histological or cytological confirmation of locally advanced or metastatic castrate resistant prostate cancer who have progressive disease at the time of entry demonstrated either by Response Evaluation Criteria in Solid Tumors (RECIST) (measurable disease) or by two subsequently increasing Prostate-specific antigen (PSA) values obtained at least one week apart. Arm 3 will include non-mCRPC patients. The patient populations in the dose expansion phase will be as follows:
•Arm 1 Prostate cancer patients with prior second generation anti-hormonal therapy (examples: abiraterone, enzalutamide, TAK 700) without response (disease progression in ≤4 months or Stable Disease (SD) but Prostate-specific antigen (PSA) level did not decline ≥50%).
•Arm 2 Prostate cancer patients with intial response to second generation anti-hormonal therapy (examples: abiraterone, enzalutamide, TAK 700), but later relapsed. Disease relapse would be defined as progressive disease at the time of entry demonstrated either by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (measurable disease) or by two subsequently increasing Prostate-specific antigen (PSA) values obtained at least one week apart. If clinically meaningful benefits have been identified in a non-mCRPC patient population during the escalation phase, a potential third expansion arm may be considered.
•Arm 3 Patients with a non-mCRPC type solid tumour such as locally advanced or metastatic breast, bladder, ovarian, gastric or salivary duct carcinomas.
•Aged at least 18 years
+9 more criteria

Exclusion Criteria

•Patients who have been treated with most recent chemotherapy or investigational drugs ≤21 days or 5 half-lives (whichever is longer) for enrolment, and/or who have National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) v4.03 Grade 1 treatment-related side effect, with the exceptions of alopecia, should not be enrolled. For further details, please refer to the following link: http://evs.nci.nih.gov/ftp1/CTCAE/About.html.
•Patients who received chemotherapy regimens given either continuously or weekly with limited potential for delayed toxicity or palliative/focal radiotherapy within the last 2 weeks or any other radiotherapy or immunotherapy within 3 weeks of the first dose of study treatment.
•Major surgery (excluding placement of vascular access) ≤21 days of beginning of the study drug or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
•Any of the following cardiac criteria: - Congestive heart failure (CHF) per New York Heart Association (NYHA) classification \> Class II (see Appendix C) - Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy - Unstable angina or new-onset angina - QTcF \>470 ms on screening electrocardiogram (ECG) by Fredericia's formula.
•Patients with leptomeningeal metastases

Locations (4)

Research Site

Sarasota, Florida, United States

Research Site

Nashville, Tennessee, United States

Research Site

Milwaukee, Wisconsin, United States

Research Site

London, United Kingdom

Key Dates

Start Date

May 1, 2014

Primary Completion Date

March 1, 2016

Completion Date

March 1, 2016

Last Updated

July 14, 2016

Enrollment

ACTUAL participants

Conditions

Advanced Solid Tumours With Androgen Receptor Pathway as a Potential Factor

Interventions

AZD5312

DRUG