Study to Assess the Safety and Preliminary Efficacy of AZD0156 at Increasing Doses Alone or in Combination With Other Anti-cancer Treatment in Patients With Advanced Cancer

NCT02588105 | Completed Phase 1

• 2 other identifiers: D6500C000012015-002572-25
• Study Type: interventional
• Target: 84
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this study is to determine whether AZD0156 is safe, what is the best dose to give, and how it is processed by the body when given alone or in combination with other agents. The study will also collect some initial information about how effective it is.

Conditions

Advanced Solid Tumours

Keywords

Phase I, open label study; safety and efficacy of AZD0156; ATM inhibitor

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability - Number of patients experiencing adverse events

  Safety and tolerability of AZD0156 alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents as assessed through collection of Adverse Event, Serious Adverse Event, Clinical Chemistry/Haematology/Coagulation/Vital Signs and ECG

  Informed consent until end of Safety Follow-up (approximately 6 months)

Secondary Outcomes (14)

• Anti-tumour activity assessed through tumour measurements

  Baseline and then every 6 weeks until Safety follow-up (approximately 6 months)

• Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition

  From baseline until 21 days of combination therapy (Approximately 11 assessments)

• Changes in the number of CTCs (Circulating Tumour Cells)

  From baseline until 21 days of combination therapy (Approx 6 assessments)

• Changes in the level of total ctDNA (Circulating tumour DNA)

  From baseline until 21 days of combination therapy (approximately 11 assessments)

• Measure maximum plasma concentration (Cmax)

  From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

Study Arms (1)

Safety and Tolerability

EXPERIMENTAL

All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability

Drug: AZD0156; Drug: Olaparib; Drug: irinotecan; Drug: Fluorouracil; Drug: Folinic Acid

Interventions

AZD0156 DRUG

All patients will receive AZD0156 as a monotherapy or in combination to assess safety and tolerability.

Safety and Tolerability

Olaparib DRUG

Module 1 combination with olaparib

Also known as: AZD2281, Lynparza

Safety and Tolerability

irinotecan DRUG

Module 2 combination with irinotecan/FOLFIRI

Also known as: Camptosar

Safety and Tolerability

Fluorouracil DRUG

Module 2 combination with irinotecan/FOLFIRI

Also known as: 5-FU, Adrucil

Safety and Tolerability

Folinic Acid DRUG

Module 2 combination with irinotecan/FOLFIRI

Also known as: leucovorin

Safety and Tolerability

Eligibility Criteria

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

You may qualify if:

• Confirmation of locally advanced/metastatic cancer. Refractory or resistant to standard therapy, or have no effective standard
• Aged at least 18 yrs
• Reasonable health (performance status 0 or 1), stable over the previous 2 weeks
• Females who can have children must use contraception; have a negative pregnancy test, \& not be breast feeding

You may not qualify if:

• Prior treatment with an ATM inhibitor
• Past medical history of an inflammatory type(interstitial) lung disease or current inflammatory lung disease
• Radiotherapy within the last 4 weeks, except palliative radiotherapy for bone pain relief
• Prior treatment with drugs that may cause lung damage
• Poor of lung function
• History/presence of muscle weakness or abnormal blood tests relating to muscle function
• Cancer affecting the spinal cord and/or brain unless asymptomatic and stable
• Any evidence of severe or uncontrolled diseases, active bleeding,kidney transplant, or active infection including liver infections (hepatitis B, hepatitis C) and human immunodeficiency virus (HIV).
• Evidence of severe lung infections
• Receiving, or having received during the four weeks prior to starting study treatment other chemotherapy treatment for your cancer
• Treatment with certain doses of steroids during the two weeks prior to starting study treatment
• A known sensitivity to AZD0156 or any of its components
• Treatment with any unapproved medicine within 28 days prior to starting study treatment
• Receiving, or having received medications, herbal supplements and/or foods that significantly affect how your liver works
• Low numbers of certain blood cells

Sponsors & Collaborators

• AstraZeneca: lead
• Syneos Health: collaborator

Study Sites (5)

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

New York, New York, 10033, United States

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• Smith G, Alholm Z, Coleman RL, Monk BJ. DNA Damage Repair Inhibitors-Combination Therapies. Cancer J. 2021 Nov-Dec 01;27(6):501-505. doi: 10.1097/PPO.0000000000000561.

  PMID: 34904813 DERIVED

• Riches LC, Trinidad AG, Hughes G, Jones GN, Hughes AM, Thomason AG, Gavine P, Cui A, Ling S, Stott J, Clark R, Peel S, Gill P, Goodwin LM, Smith A, Pike KG, Barlaam B, Pass M, O'Connor MJ, Smith G, Cadogan EB. Pharmacology of the ATM Inhibitor AZD0156: Potentiation of Irradiation and Olaparib Responses Preclinically. Mol Cancer Ther. 2020 Jan;19(1):13-25. doi: 10.1158/1535-7163.MCT-18-1394. Epub 2019 Sep 18.

  PMID: 31534013 DERIVED

MeSH Terms

Interventions

AZD0156; olaparib; Irinotecan; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Matthew Krebs, BMedSci, BM, BS, PhD, MRCP

  The Christie Hospital, Manchester, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 27, 2015
• Study Start: November 10, 2015
• Primary Completion: September 13, 2019
• Study Completion: July 26, 2022
• Last Updated: September 19, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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

US (2); KR (1); ES (1); GB (1)