Phase I AZD2281/Cisplatin in Advanced Solid Tumour Patients

A Phase I Open Label, Multi Centre Study of AZD2281 Administered Orally in Combination With Cisplatin, to Assess the Safety and Tolerability in Patients With Advanced Solid Tumours

A Phase I study to assess the safety and tolerability of AZD2281 in combination with Cisplatin in patients with advanced Solid Tumours. This is an open label-dose finding; to establish the maximum tolerated dose of AZD2281 combined with Cisplatin in patients with advanced solid tumours. Approximately 50 (max 60) patients from 2 countries will be enrolled

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AZD2281; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 8035
    • Research Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Life expectancy of at least 12 weeks
• Histologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent
• Patients with measurable or non measurable disease according to RECIST

Exclusion Criteria:

• Less than 28 days from active therapy (ie any treatment used to treat the disease) or high dose radiotherapy
• Brain Metastases or spinal cord compression unless irradiated at least 4 weeks before entry and stable without steroid treatment for >1 week
• Persistent CTCAE Grade 2 or greater toxicities (excluding alopecia) caused by prior therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions.

Drug: AZD2281; Tablets Oral BID; Other Names: Olaparib; Lynparza; Drug: Cisplatin; IV every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of AZD2281 in combination with Cisplatin (eg Adverse Events, Pharmacokinetic for AZD2281, overall response rate) to patients with advanced solid tumours.	Weekly visits for routine monitoring visits

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare exposure to AZD2281 when given alone and in combination with Cisplatin (Only in patients receiving continuous dosing of AZD2281).	PK samples taken at visit 2 and 3
To make a preliminary assessment of the anti-tumour activity of AZD2281 when given in combination with Cisplatin, by measuring overall objective response rate.	Assessed at screening, visit 9, and at end of every 2 cycles

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Jane Robertson, BSc, MBCHB, MD, AstraZeneca; Principal Investigator: Judy E Garber, Dana-Farber Cancer Institute; Principal Investigator: J Ballmana Gelpi, Vall d'Hebron

Publications and helpful links

Helpful Links

• D0810C00021 redacted protocol
• CSR_Synopsis_D0810C00021.pdf

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): December 7, 2023

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 30, 2008
• First Posted (Estimated): October 31, 2008

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Advanced solid tumours; BRCA1; Poly(ADP ribose) polymerases; homologous deficiency
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: D0810C00021; 2008-000062-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing 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
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP