Study to Assess the Safety and Tolerability of a PARP Inhibitor in Combination With Carboplatin and/or Paclitaxel

NCT00516724 | Completed Phase 1

• 3 other identifiers: KU36-96D0810C000042007-000939-26
• Study Type: interventional
• Target: 189
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to identify a safe and tolerable dose of the drug KU-0059436 that can be given in combination with carboplatin and/or Paclitaxel chemotherapy.

Conditions

Triple Negative Metastatic Breast Cancer; Advanced Ovarian Cancer; Carboplatin; Paclitaxel

Keywords

malignant solid tumours; Poly(ADP ribose) polymerases

Outcome Measures

Primary Outcomes (1)

• To establish the maximum tolerated dose (MTD) of KU 0059436 in combination with Paclitaxel/Carboplatin

  assessed at each visit

Secondary Outcomes (1)

• To identify the dose limiting toxicity of the combination therapy

  assessed at each visit

Study Arms (3)

1

EXPERIMENTAL

Carboplatin + KU-0059436

Drug: KU-0059436 (AZD2281)(PARP inhibitor); Drug: Carboplatin

2.

EXPERIMENTAL

Paclitaxel + KU-0059436

Drug: KU-0059436 (AZD2281)(PARP inhibitor); Drug: Paclitaxel

3.

EXPERIMENTAL

Paclitaxel, Carboplatin + KU-0059436

Drug: KU-0059436 (AZD2281)(PARP inhibitor); Drug: Paclitaxel + Carboplatin

Interventions

KU-0059436 (AZD2281)(PARP inhibitor) DRUG

oral

Also known as: Olaparib

1

Carboplatin DRUG

intravenous injection

Also known as: CBDCA, Paraplatin®

1

Paclitaxel DRUG

Intravenous injection

2.

Paclitaxel + Carboplatin DRUG

Intravenous injection

3.

Eligibility Criteria

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

You may qualify if:

• Male or female patients with a histologically or cytologically diagnosed malignant solid tumour
• Adequate bone marrow, hepatic and renal function
• Performance status of no more than 2 ( ECOG scale).

You may not qualify if:

• Any chemotherapy, radiotherapy ( except palliative), endocrine or immunotherapy within 4 weeks prior to entry
• Major surgery with 4 weeks of entering the study and must have recovered from effects of the major surgery
• More than two previous courses of platinum-containing chemotherapy
• Heavily pre-treated patients(\> 2 courses of previous chemotherapy and/or extensive irradiation leading to bone marrow deficiency) will be excluded from the study

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Brussels, 1090, Belgium

Location

Research Site

Amsterdam, 1066 EC, Netherlands

Location

Research Site

Rotterdam, 3015, Netherlands

Location

Research Site

London, SM2 5NG, United Kingdom

Location

Related Publications (3)

• van der Noll R, Jager A, Ang JE, Marchetti S, Mergui-Roelvink MWJ, Lolkema MP, de Jonge MJA, van der Biessen DA, Brunetto AT, Arkenau HT, Tchakov I, Beijnen JH, de Bono JS, Schellens JHM. Phase I study of continuous olaparib capsule dosing in combination with carboplatin and/or paclitaxel (Part 1). Invest New Drugs. 2020 Aug;38(4):1117-1128. doi: 10.1007/s10637-019-00856-7. Epub 2019 Oct 30.

  PMID: 31667659 DERIVED

• van der Noll R, Jager A, Ang JE, Marchetti S, Mergui-Roelvink MWJ, de Bono JS, Lolkema MP, de Jonge MJA, van der Biessen DA, Brunetto AT, Arkenau HT, Tchakov I, Beijnen JH, De Greve J, Schellens JHM. Phase I study of intermittent olaparib capsule or tablet dosing in combination with carboplatin and paclitaxel (part 2). Invest New Drugs. 2020 Aug;38(4):1096-1107. doi: 10.1007/s10637-019-00857-6. Epub 2019 Oct 21.

  PMID: 31637669 DERIVED

• Shamseddine AI, Farhat FS. Platinum-based compounds for the treatment of metastatic breast cancer. Chemotherapy. 2011;57(6):468-87. doi: 10.1159/000334093. Epub 2012 Jan 10.

  PMID: 22248721 DERIVED

Related Links

• KU36-96\_CSR\_Synopsis
• revised\_CSP9
• Study Results

MeSH Terms

Interventions

olaparib; Carboplatin; Paclitaxel; CP protocol

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Jane Robertson, BSc, MBCHB, MD

  AstraZeneca

  STUDY DIRECTOR

• Dr Johann de Bono, MD

  Cancer Research UK, The Institute of Cancer Research, London, UK

  PRINCIPAL INVESTIGATOR

• Prof Jan HM Schellens

  The Netherlands Cancer Institute, Amsterdam, The Netherlands

  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

Study Record Dates

• First Submitted: August 13, 2007
• First Posted: August 15, 2007
• Study Start: June 22, 2007
• Primary Completion: January 4, 2013
• Study Completion: April 11, 2024
• Last Updated: April 11, 2025

Record last verified: 2025-04

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

GB (1); NL (2); BE (1)