Mass balance Study of Plitidepsin Administered Intravenously Over 3 Hours to Patients with Advanced Cancer
- Conditions
- advanced cancer10027655cancer
- Registration Number
- NL-OMON42098
- Lead Sponsor
- PharmaMar
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 6
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 maximum of ten days.
3) Patients with histologically/cytologically confirmed diagnosis of advanced cancer (i.e., solid tumors, lymphomas and multiple myelomas) refractory to standard therapy or for whom no standard therapy exists or patients who have refused standard therapy.
4) Age >= 18 years.
5) Body Surface Area (BSA) >= 1.4 m².
6) Eastern Cooperative Oncology Group (ECOG) performance status (PS) score < 2.
7) Adequate bone marrow, renal, hepatic, and metabolic function (assessed <= 7 days before inclusion in the study):
a) Platelet count >= 100 x 109/L, hemoglobin >= 5.58 mmol/L and absolute neutrophil count (ANC) >= 1.0 x 109/L.
b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 x the upper limit of normal (ULN).
c) Total bilirubin <= 1.0 x ULN or direct bilirubin <= 1.0 x ULN when total bilirubin is above the ULN.
d) Calculated creatinine clearance (CrCl) >= 45 mL/minute (by means of Cockcroft and Gault*s formula).
e) Creatine phosphokinase (CPK) <= 2.5 x ULN.
f) Albumin >= 30 g/L.
8) Recovery to grade <= 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and peripheral neuropathy grade <= 2).
9) Left ventricular ejection fraction (LVEF), by echocardiogram (ECHO) or multiple-gated acquisitions (MUGA) >= 50%.
10) Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include: intrauterine contraceptive device (IUD), oral contraceptives, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).
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) Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 x ULN in two different determinations performed one week apart).
e) Limitation of the patient*s ability to comply with the treatment or follow-up protocol.
f) Any other major illness that, in the Investigator*s judgment, will substantially increase the risk associated with the patient*s participation in this study.
2) Symptomatic, progressive or corticosteroid-requiring documented brain metastases or leptomeningeal disease. Controlled and stable brain metastases without steroids are allowed.
3) Patients diagnosed with CNS tumors or leukemia.
4) Women who are pregnant or breast-feeding.
5) High transfusion requirements (> 2 packages of red blood cells and/or 1 platelet transfusion) in the 30 days prior to inclusion in the study.
6) Chemotherapy, radiotherapy, immunotherapy, or molecular targeted cancer therapy within the previous four weeks of the given drug, prior to the start of trial medication or concomitantly within this trial. This restriction does not apply to steroids and bisphosphonates.
7) Major surgical procedure within the last eight weeks prior to the start of trial medication.
8) Clinically relevant non-malignant disease, which in the Investigator's opinion would exclude the subject from the trial, such as significant cardiovascular, pulmonary, endocrine, renal and neurological disease or psychiatric disorder.
9) Known hypersensitivity to any of the excipients used.
10) Participation in another clinical trial 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. The total radioactivity exposure from the current study and the previous 14C study must be less than 5 mSv.
11) Tumoral or other conditions affecting the gastrointestinal tract or close to the gastrointestinal tract that may be expected to induce total or partial occlusion of the gastrointestinal transit.
12) Presence of, or history of, inflammatory bowel disease or digestive tract fistulae.
13) Significant constipation (defined as <1 deposition every 2 days or need for laxatives)
14) Any condition resulting in clinically evident obstruction of the urinary tract.
15) A history or regular use of tobacco- or nicotine-containing products within three months prior to screening.
16) Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from two days prior to the first dose of study medication.
17) History of alcoholism.
18) Any condition that could interfere with the accurate assessment and recovery of radiocarbon [14C].
19) Unwillingness or inability to follow the procedures outlined in the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• To obtain the mass balance of plitidepsin in adult patients with advanced<br /><br>cancer.<br /><br>• To identify the metabolites of plitidepsin formed in adult patients with<br /><br>advanced cancer.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• To determine, if possible, the concentration of as many plitidepsin<br /><br>metabolites as feasible in body fluids.<br /><br>• To assess, if possible, whether cytochrome P450 (CYP) and/or UDP<br /><br>glucoronosyltransferase (UGT) enzyme genotypes, responsible for the metabolism<br /><br>of plitidepsin, are related to major differences in the availability of<br /><br>plitidepsin.<br /><br>• To characterize the safety profile and feasibility of plitidepsin in patients<br /><br>with advanced cancer.</p><br>