Clinical trial NCT01380249: PDM08 Clinical Trial in Advanced Solid Tumors
Official title: Phase I Study, Open, Dose Escalation, in Adult Patients With Advanced Solid Tumours, to Evaluate Tolerability, Pharmacokinetics and Pharmacodynamics of PDM08 Administered Twice a Week Cycles of 4 Weeks.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Solid Tumours
Keywords: Phase I
Phase I multiple doses
PDM08
Cancer Treatment
Pharmacokinetics and Pharmacodynamics
Advanced Solid Tumors
Prodimed
Lead sponsor: Prodimed S.A.
Sponsor class: OTHER
First posted: 2011-06-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number and grade of adverse events by participant related to PDM08.
timeFrame: 6 weeks for each cohort.
measure: Dose limiting toxicity (DLT)
timeFrame: 6 weeks.
Secondary outcomes:
measure: AUC
timeFrame: 4 weeks
measure: Cmax
timeFrame: 4 weeks
measure: Volume of distribution (Vd)
timeFrame: 4 weeks
measure: Plasma half-life of PDM08 (T ½)
timeFrame: 4 weeks
measure: Changes in tumour size by Computed Tomography (CT)
timeFrame: 6 weeks
measure: Tumour activity: Positron emission tomography (PET)
timeFrame: 6 weeks
measure: Myeloid cells in peripheral blood.
timeFrame: 6 weeks
measure: B and T lymphocytes and NK cells Populations
timeFrame: 6 weeks
measure: Serum Immunoglobulins
timeFrame: 6 weeks
measure: Complement components: C3 and C4; and C-Reactive Protein (CRP)
timeFrame: 6 weeks
measure: Serum cytokines
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Hospital Universitario La Paz
name: Jorge Barriuso, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: