advanced cancer solid tumors
Conditions
Interventions
This is a Phase I, open-label, uncontrolled, pharmacology study to
characterize the mass balance of PM01183 administered as 1 hour (h) intravenous
(i.v.) infusion every three weeks (q3wk) (one cycle
subsequent doses of PM01183, up
to a maximum of eight cycles, will not be radio-labelled.
Sponsors
Pharma Mar
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Voluntarily signed and dated written informed consent (IC) obtained from the patient prior to any specific study procedure. 2) Patient*s availability to stay in the research unit up to a minimum of eight days. 3) Patients with histologically/cytologically confirmed solid malignant disease (not recorded in the exclusion criteria), for which no standard therapy would reasonably be expected to result in cure or palliation. 4) Age >= 18 years. 5) Body Surface Area (BSA) >= 1.56 m2. 6) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 1.5 x 10^9/L. b) Platelet count >= 100 x 10^9/L. c) Hemoglobin >= 9 g/dL (5.6 mmol/L). d) Albumin >= 3.0 g/dL. e) Calculated creatinine clearance (CrCL) >= 30 mL/min (using the Cockcroft and Gault*s formula). f) Serum total bilirubin ULN and as long as total bilirubin
Exclusion criteria
Exclusion criteria: 1) Concomitant diseases/conditions: a) History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure within the last 12 months. b) Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade >= 2. c) Active uncontrolled infection. d) Limitation of the patient*s ability to comply with the treatment or follow-up protocol. e) Any other major illness that, in the Investigator*s judgment, will substantially increase the risk associated with the patient*s participation in this study. This includes but is not limited to, any significant disease such as significant cardiovascular, pulmonary, endocrine, renal, neurological or psychiatric disorder. 2) Symptomatic, progressive or corticosteroid-requiring documented brain metastases or leptomeningeal disease (controlled and stable or non-progressing brain metastases without steroids are allowed). 3) Patients with the following tumors: 1) Concomitant diseases/conditions: a) History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure within the last 12 months. b) Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade >= 2. c) Active uncontrolled infection. d) Limitation of the patient*s ability to comply with the treatment or follow-up protocol. e) Any other major illness that, in the Investigator*s judgment, will substantially increase the risk associated with the patient*s participation in this study. This includes but is not limited to, any significant disease such as significant cardiovascular, pulmonary, endocrine, renal, neurological or psychiatric disorder. 2) Symptomatic, progressive or corticosteroid-requiring documented brain metastases or leptomeningeal disease (controlled and stable or non-progressing brain metastases without steroids are allowed). 3) Patients with the following tumors: a) Colorectal cancer. b) Primary CNS tumors. 4) Women who are pregnant or breast-feeding. 5) High transfusion requirements (> two packages or units of red blood cells and/or one platelet transfusion) within 30 days prior to inclusion in the study. 6) Chemotherapy, radiotherapy, immunotherapy or molecular targeted cancer therapy within four weeks prior to the start of PM01183 administration (six weeks for mitomycin C, nitrosourea therapy, temozolomide and other minor groove binders). This restriction does not apply to steroids and/or bisphosphonates. 7) Major surgical procedure within the last eight weeks prior to the first PM01183 administration. 8) Wide-field radiotherapy (> 25% of bone marrow [BM] reserve) within 12 months prior to administration of PM01183 (pelvic radiation is considered 25% BM reserve). 9) Known hypersensitivity to any of the excipients used. 10) Participation in another clinical study or concomitant treatment with any investigational product in the 30-day period prior to inclusion in the study and/or participation in a 14C study within the last six months prior to screening for the current study. Total radioactivity exposure from the current study and any previous 14C study must not exceed 5 mSv. 11) Tumoral or other conditions affecting the gastrointestinal (GI) tract or near the GI tract expected to induce total or partial occlusion of the GI transit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To obtain the mass balance and the time course of excretion of PM01183 in adult patients with advanced cancer. - To identify PM01183 metabolites formed in adult patients with advanced cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To determine, if feasible, the concentration of as many PM01183 metabolites as possible in body fluids. - To evaluate, if possible, whether cytochrome P450 (CYP) and/or nuclear receptors and drug transporter genotypes, responsible for PM01183 metabolism, are related to major differences in the patient*s exposure to PM01183. - To characterize the safety profile and feasibility of PM01183 in patients with advanced cancer. | — |
Countries
Netherlands
Outcome results
None listed