advanced solid tumors
Conditions
Interventions
The dose escalation phase will follow a traditional 3+3 design in two cohorts.
In cohort 1 melphalan will be escalated on the background of an effective
olaparib dose. If after escalating melphalan
Sponsors
Nederlands Kanker Instituut
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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): 10.0 g/dl (6.2 mmol/l) -absolute neutrophil count >1.5 x 109/L -platelets >100 x 109/L; Biochemistry: -Total bilirubin : = 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point: • Recommended phase II dose determined by the dose limiting toxicity (DLT) graded using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end points: • Pharmacokinetics of the combination of olaparib and melphalan in two cohorts • Pharmacodynamics: measuring PARP activity and γH2AX-RAD51 foci (plasma and potential tumor) • Assess objective response rates via RECIST in patients with measurable disease | — |
Countries
Netherlands
Outcome results
None listed