PDM08 Clinical Trial in Advanced Solid Tumors

Prodimed S.A.22 enrolled

Overview

This phase I study in adult patients with advanced solid tumours is designed to evaluate toxicity, drug exposure (pharmacokinetics) and drug action (pharmacodynamics) of a new molecule, PDM08, administered twice a week cycles of 4 weeks. This drug has shown antitumoral activity in several murine cancer models.

Phase I study, open, dose escalation, in adult patients with advanced solid tumours, to evaluate tolerability, pharmacokinetics and pharmacodynamics of ascending PDM08 doses administered twice a week cycles of 4 weeks. After checking the safety of the first drug doses, a new dose escalation was proposed and approved by the Ethic Committee and the Medicines Agency. This clinical trial is carried out in adult patients with advanced solid tumours whose disease has progressed despite standard therapy, or for which there is no standard antineoplastic therapy, or are refractory to it. In pharmacodynamic non clinical studies, PDM08 presented antitumour activity against different tumour models including, renal, colon, lung, prostate and breast cancer models.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malignant Solid Tumours

Interventions

PDM08DRUG

To assess the tolerability and safety of increasing multiple doses administration of PDM08: 560 μg, 1.12, 2.24, 3.5, 14, 28 and 56 mg administered twice a week for four weeks in patients with advanced solid tumours for which there is no standard therapy or they are refractory to it.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Population: Adult patients with advanced solid tumours whose disease has progressed despite standard therapy, or for which there is no standard antineoplastic therapy, or are refractory to it. * Informed consent must be obtained for each patient, in accordance with the guideline for Good Clinical Practice (GCP) of the International Conference of Harmonization (ICH) and with the local requirements. * Malignant tumour, histologically or cytologically demonstrated. * Patients age equal or greater than 18 years. * Patients must not have an ECOG\>2 (ECOG 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours) * The life expectancy of the patient should be superior to 3 months. * Bilirubin\<1,5 times the laboratory upper limit. * AST and ALT less than 2,5 times the laboratory upper limit, In case of liver metastases to a value less than 5 times the laboratory upper limit. * Women in fertile age: a pregnant test must be carried out. * Men and women in fertile age must commit to to practice one method of birth control during their participation in the trial, and 30 days after the administration of the last dose of the experimental drug. * The patient should have renal function parameters (creatinine) not exceeding 1.5 times the normal upper limit. * The patient must present a hemoglobin \> 9 mg/dL. * The patient must show basal platelet count \> 100.000 /mm3. * Specific criteria: * Patients included in the expansion cohort must present a measurable disease by RECIST criteria 1.1, and disease progression in the last 6 months. * Patients who agree to enter into the pharmacodynamic tumour tissue substudy should present accessible tissue to carry out the biopsy safely. Exclusion Criteria: * Patients who have received chemotherapy, radiotherapy, immunotherapy or investigational drugs for their disease within 4 weeks prior to PDM08 first dose. * Patients who have had surgery within 4 weeks before treatment. * Patients with untreated brain metastases. * Patients who are pregnant or breast-feeding. * Those patients who present an intercurrent non-controlled disease including, but not limited to, active infections, cicatrization problems, congestive heart failure, unstable angina, cardiac arrhythmia, pulmonary disease with non controlled symptoms, non controlled psychiatric disorders or social situations that may affect the compliance with the requirements of the study.

Locations (1)

Hospital Universitario La Paz

Madrid, Madrid, Spain

Outcomes

Primary Outcomes

Number and grade of adverse events by participant related to PDM08.

Drug safety will be measured by the number and grade of adverse events, by participant, related to the drug in study (PDM08) in the cohorts studied: 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks. The drug will be administered twice a week for four weeks. Safety and tolerability will be measured considering the adverse events occurred, by participant, related with the drug in study, PDM08, at each cohort.

Time frame: 6 weeks for each cohort.

Dose limiting toxicity (DLT)

Drug tolerability will be assessed by determining the DLT. It will be determined for each cohort (increasing multiple doses of PDM08): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks). Dose Limiting Toxicity will be considered the dose that produces adverse events of a severity grade 3 or greater, related to the drug in study (PDM08) in the classification specified in the list of Toxicity Criteria of the National Cancer Institute (CTCAE v04.03).

Time frame: 6 weeks.

Secondary Outcomes

AUC

Blood sampling collected on Day 1 and 25 of each cohort cycle.Cohorts (doses): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks. Blood collection scheme: - Dose of 560 μg and 1.12 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle. - Doses of 2.24 mg, 3.5 mg, 14 mg, 28 mg, and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle. Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Time frame: 4 weeks

Cmax

Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(doses): 560 μg, 1.12 mg, 2.24 mg, 3.5 mg and 14 mg, 28 mg and 56 mg administered twice a week for four weeks. Blood collection scheme: * Dose of 560 μg and 1.12 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle. * Dose of 3.5 mg and 14 mg, 28 mg and 56 mg: 0,0.25, 1, 2, 4, 8, 12, 16 and 24 hours post-dose, on day 1 and day 25 of each cycle. Pharmacokinetic parameters will be expressed as mean ± standard deviation and confidence interval 95%. Linearity will be analyzed.

Data from ClinicalTrials.gov

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