A phase I study to determine the maximum tolerable dose (MTD) of weekly carboplatin with the Wee1 inhibitor AZD1775 in patients with p53 mutated solid tumors.

Withdrawn

• Conditions: cancer in organs; Solid tumors; 10027476

• Registration Number: NL-OMON45937
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

1. Histological or cytological proof of advanced p53 mutated cancer, pre-treated with maximally one line of systemic chemotherapy in the advanced setting and any line of hormonal or immunotherapy for advanced disease, and potentially benefitting from carboplatin-AZD1775 combination therapy (prior (neo-)adjuvant chemotherapy is accepted and does not count as one line, since administered in early stage disease);
5. Able and willing to undergo blood sampling for PK and PD analysis;
6. Able and willing to undergo a tumor biopsy (if p53 status is already known, tumor biopsy is still mandatory)
8. Evaluable disease according to RECIST 1.1 criteria;

Exclusion Criteria

1. Any treatment with investigational drugs within 28 days prior to receiving the first dose of investigational treatment; or 21 days for standard (neo-)adjuvant chemotherapy, hormonal and immunotherapy;
6. Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia.
8. Patient has had prescription or non-prescription drugs or other products known to be metabolized by CYP3A4, or to inhibit or induce CYP3A4 that cannot be discontinued two weeks prior to Day 1 of dosing and withheld throughout the study until 1 week after the last dose of study medication.
17. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) >= Class 2.
o Unstable angina pectoris
o Congestive heart failure
o Acute myocardial infarction
o Conduction abnormality not controlled with pacemaker or medication

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Maximum tolerable dose of the combination therapy of weekly carboplatin with<br /><br>the Wee-1 inhibitor AZD1775</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Preliminary response rate<br /><br>Pharmacokinetics</p><br>