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Phase I Study to Assess Safety of AZD6738 Alone and in Combination With Radiotherapy in Patients With Solid Tumours (Patriot)

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ClinicalTrials.gov Identifier: NCT02223923
Recruitment Status : Unknown
Verified October 2019 by Royal Marsden NHS Foundation Trust.
Recruitment status was:  Active, not recruiting
First Posted : August 22, 2014
Last Update Posted : April 8, 2020
Sponsor:
Collaborators:
AstraZeneca
Cancer Research UK
RM/ICR Biomedical Research Centre
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE August 21, 2014
First Posted Date  ICMJE August 22, 2014
Last Update Posted Date April 8, 2020
Study Start Date  ICMJE July 2014
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2014)
Identifying the maximum tolerated dose (MTD) of AZD6738 as a single-agent; and in combination with palliative radiation schedules. [ Time Frame: 4 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2014)
  • Determining causality of each adverse event in relation to AZD6738 and grading severity according to CTCAE version 4; [ Time Frame: 4 weeks ]
  • Single and multiple dose pharmacokinetics: measurement of plasma levels of AZD6738 at pre-defined intervals in the dose-escalation part of the study in order to establish pharmacokinetic parameters; [ Time Frame: Day 0 and Day 1 ]
  • Any response (stable disease, partial response or complete response) in any of the patients by physical, tumour marker and/or radiographic assessments of tumours as determined by RECIST 1.1. [ Time Frame: 8 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study to Assess Safety of AZD6738 Alone and in Combination With Radiotherapy in Patients With Solid Tumours
Official Title  ICMJE A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor (AZD6738) as a Single Agent and in Combination With Palliative Radiation Therapy in Patients With Solid Tumours
Brief Summary

This study will investigate the use of a new drug targeting the DNA repair pathway AZD6738, an ATR inhibitor). Many tumours have lost important DNA repair functions and rely more heavily on a few remaining repair pathways to survive. Preclinical studies indicate that, in these tumours, preventing the function of the remaining pathways will lead to tumour cell death, while sparing normal cells. This study aims to investigate the safety and tolerability of the new drug in patients with advanced cancer, as well as in combination with palliative radiotherapy, where the drug may increase the effectiveness of radiotherapy by preventing repair of the radiationinduced DNA damage. As the drug has only been given to a small number of patients, the study will focus on safety and finding the correct dose to proceed to further studies, although preliminary signs of drug activity will also be examined.

The initial part of the study will administer increasing doses of the drug to groups of patients with advanced cancer who have no standard anticancer treatment options available. Testing will establish whether the drug levels in the body and tumour are adequate for the drug to have an effect, and any toxicity will be assessed. After the recommended dose is established, the recommended dose schedule will be stablished by trialing different schedules. Participants will be tested to see if their tumours lack the main DNA repair pathway (those who are predicted to have a better response to this drug). Finally, the drug will be given to patients with advanced cancer who require a course of radiotherapy for symptom control - the drug will be tested at different doses and with different doses of radiotherapy.

Side effects will be monitored and tests will establish whether the drug is enhancing the radiotherapy effect in the tumours or normal tissues.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumour Refractory to Conventional Treatment
Intervention  ICMJE
  • Drug: AZD6738
  • Radiation: Palliative radiotherapy
Study Arms  ICMJE
  • Experimental: Dose Escalation
    AZD6738 PO 20 to 380mg BD increasing
    Intervention: Drug: AZD6738
  • Experimental: AZD6738 - Expansion Phase
    AZD6738 starting dose and regimen to be determined in dose escalation phase
    Intervention: Drug: AZD6738
  • Experimental: AZD6738 + Radiotherapy (Head and Neck)
    AZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy)
    Interventions:
    • Drug: AZD6738
    • Radiation: Palliative radiotherapy
  • Experimental: AZD6738 + Radiotherapy (Abdomen / Pelvis)
    AZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy)
    Interventions:
    • Drug: AZD6738
    • Radiation: Palliative radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 21, 2014)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically documented solid tumour refractory to conventional treatment
  • Evidence of measurable or evaluable disease by RECIST 1.1
  • Age must be 18 years or over.
  • ECOG performance status 0-1 (part A); 0-2 (parts B and C)
  • Life expectancy of at least 3 months.
  • Patients must have normal organ and bone marrow function measured within 7 days prior to administration of study treatment as defined below:
  • Signed informed consent indicating that the subject is aware of the neoplastic nature of their disease and have been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
  • Willing and able to comply with scheduled visits, tissue sampling, treatment plan, and laboratory tests.
  • Able to swallow, absorb and retain oral medication.

Exclusion Criteria:

  • Therapy with any other investigational medical product (IMP) concurrently or within 28 days prior to signing of consent.
  • Pregnant or breast-feeding women.
  • Ability to become pregnant (or already pregnant or lactating).
  • Clinically significant cardiac disease including:
  • Known HIV positive or active hepatitis B or C infection
  • Uncontrolled active infection
  • Symptomatic and progressive or steroid-requiring brain metastases or leptomeningeal disease involvement.
  • Uncontrolled hypertension requiring clinical intervention, hypertension requiring 2 or more antihypertensive agents
  • Dementia or altered mental status that would prohibit informed consent.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the subject inappropriate for this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02223923
Other Study ID Numbers  ICMJE CCR4087
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Royal Marsden NHS Foundation Trust
Study Sponsor  ICMJE Royal Marsden NHS Foundation Trust
Collaborators  ICMJE
  • AstraZeneca
  • Cancer Research UK
  • RM/ICR Biomedical Research Centre
Investigators  ICMJE
Principal Investigator: Kevin Harrington, MBBS MRCP FRCR Institute of Cancer Research, United Kingdom
Principal Investigator: Martin Forster University College London Hospitals
PRS Account Royal Marsden NHS Foundation Trust
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP