A pilot phase I open-label study to assess the safety and tolerability of Olaparib, a poly-(ADP-ribose)polymerase (PARP) inhibitor, in combination with melphalan for the treatment of patients with homologous recombination deficient metastatic solid tumors

• Conditions: advanced; solid tumors; 10027655

• Registration Number: NL-OMON37339
• Lead Sponsor: ederlands Kanker Instituut

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 60

Inclusion Criteria

- Before patient registration, written informed consent must be given
- Male or female patients with a histologically or cytologically diagnosed metastatic or locally advanced malignant solid tumor having hallmarks of BRCA-1 or -2 deficiency:
o BRCA-1 or -2 mutation carriers with any tumor
o Breast cancer patients with a BRCA-likeCGH tumor
- Patients must have progressed despite standard therapy.
- Age > 18 years
- Performance status (PS): <2 (ECOG scale) and a life expectancy of at least 12 weeks
- Patients must be able to swallow oral medication.
- Female patients of childbearing age must have a negative urine or serum pregnancy test within 7 days prior to start of study.
- Laboratory requirements within 7 days prior to start of treatment:
Haematology:
-Haemoglobin >10.0 g/dl (6.2 mmol/l)
-absolute neutrophil count >1.5 x 109/L
-platelets >100 x 109/L;
Biochemistry:
-Total bilirubin : <1.25 x upper normal limit;
-AST (SGOT), ALT (SGPT) : <2.5 x upper limit of normal (ULN); in case of liver metastases < 5 * ULN
-Serum creatinine clearance >= 50 ml/min (Cockroft-Gault)
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Exclusion Criteria

- Patients having received any chemotherapy, radiotherapy (except for palliative reasons), biological therapy or investigational compound administered within four weeks prior to start of study treatment or patients not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients having symptomatic brain metastases. A scan to confirm the absence of brain metastases is not required.
- Patients having gastrointestinal disorders likely to interfere with absorption of the study drug (e.g. partial bowel obstruction or malabsorption).
- Patients should not require treatment with inhibitors or inducers of Cytochrome P450 system.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary end point:<br /><br>• Recommended phase II dose determined by the dose limiting toxicity (DLT)<br /><br>graded using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE)<br /><br>version 4</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary end points:<br /><br>• Pharmacokinetics of the combination of olaparib and melphalan in two cohorts<br /><br>• Pharmacodynamics: measuring PARP activity and &gamma;H2AX-RAD51 foci (plasma and<br /><br>potential tumor)<br /><br>• Assess objective response rates via RECIST in patients with measurable<br /><br>disease </p><br>