Malignant Solid TumoursPhase 1NCT01380249
PDM08 Clinical Trial in Advanced Solid Tumors
A Phase 1 study testing PDM08 in people with Malignant Solid Tumours, run by Prodimed S.A. at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Solid Tumours
- What is being tested?
- PDM08
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteSpain
- Study dates
- Jun 2011to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 16Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Malignant Solid Tumours
- Being tested
- PDM08
- Keywords
- Phase I, Phase I multiple doses, PDM08, Cancer Treatment, Pharmacokinetics and Pharmacodynamics, Advanced Solid Tumors, Prodimed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDM08Drug
Also called 4-amino-5-oxo-4(pyridinium-1-ylmethyl)proline D-cis, 3S,5R-1-(3-Amino-5-carboxy-2-oxopyrrolidin-3-ylmethyl)pyridinium bromide hidrobromide
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.
| Study group | Role | What they receive |
|---|---|---|
| PDM08 | Experimental | To assess the tolerability and safety of increasing multiple doses administration 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 in patients with advanced solid tumours for which there is no standard therapy or the patient is refractory to it. Receives: Drug: PDM08 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 6 weeks.
Secondary outcomes (11)
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.
Measured: 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.
Measured: 4 weeks
Volume of distribution (Vd)
Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(dose): 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 1.12 mg and 2.24 mg: 0,0.25, 1, 2, 4, 8, 12 hours post-dose, on day 1 and day 25 of each cycle.
- Dose of 2.24 mg; 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.
Measured: 4 weeks
Plasma half-life of PDM08 (T ½)
Blood sampling will be collected on Day 1 and Day 25 of each cohort cycle.Cohorts(dose): 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 2.24 mg, 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.
Measured: 4 weeks
Changes in tumour size by Computed Tomography (CT)
Changes in tumour size will be measured by CT (RECIST criteria v.1.1) at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Pharmacodynamic parameters will be tabulated as raw values and sorted by dose. Statistical analysis will be performed using ANOVA with repeated measures, including baseline values as cofactor.
Measured: 6 weeks
Tumour activity: Positron emission tomography (PET)
Changes in tumour activity will be measured by PET in each cohort on days 1, 4 11, 25, 29 and 43 of the study.
Pharmacodynamic parameters will be tabulated as raw values and sorted by dose. Statistical analysis will be performed using ANOVA with repeated measures, including baseline values as cofactor.
Measured: 6 weeks
Myeloid cells in peripheral blood.
Myeloid cells in peripheral blood (total myeloid cells, monocyte-macrophage series, granulocytes and myeloid suppressor in peripheral blood) will be measured in each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Measured: 6 weeks
B and T lymphocytes and NK cells Populations
In order to determine the function of these populations the exresion of membrane markers will be analyze; and membrane markers displayed in relation to the degree of activation of lymphocytes. These parameters will be measured at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Measured: 6 weeks
Serum Immunoglobulins
Serum Immunoglobulins and subtypes (IgG1, IgG2, IgG3, IgG4, IgM, IgA) will be measured at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Measured: 6 weeks
Complement components: C3 and C4; and C-Reactive Protein (CRP)
C3 and C4 components of the complement system, CRP, and the total activity of the classical complement pathway. measured as haemolytic capacity CH50,will be measured in serum of all the participants at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Measured: 6 weeks
Serum cytokines
Serum cytokines that will be measured will be:IL1α, IL1β, IL2, IL4, IL5, IL6, IL7, IL10, IL12, IL17, TNFα, IFNγ, G-CSF, GM-CSF, VEGF. Serum cytokines will be measured in serum at each cohort on days 1, 4, 11, 25, 29 and 43 of the study.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJun 2012
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Solid TumoursStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prodimed S.A.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jorge Barriuso, MD, PhD, Principal investigator, Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01380249
- Sponsor's protocol ID
- 2009-017133-21
- Other IDs
- 2009
- Status last verified
- Jan 2013
- First submitted
- 31 May 2011
- Last updated
- 7 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01380249
- Acronym / sponsor ID
- 2009-017133-21
- Conditions
- Malignant Solid Tumours
- Keywords
- Phase I, Phase I multiple doses, PDM08, Cancer Treatment, Pharmacokinetics and Pharmacodynamics, Advanced Solid Tumors, Prodimed
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Prodimed S.A.University, hospital or other
- Study start
- Jun 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PDM08 | Experimental | Drug: PDM08To assess the tolerability and safety of increasing multiple doses administration 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 in patients with advanced solid tumours for which there is no standard therapy or the patient is refractory to it. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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)
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PDM08Also: 4-amino-5-oxo-4(pyridinium-1-ylmethyl)proline D-cis, 3S,5R-1-(3-Amino-5-carboxy-2-oxopyrrolidin-3-ylmethyl)pyridinium bromide hidrobromideTo 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. | Drug | PDM08 |
Primary outcome
Number and grade of adverse events by participant related to PDM08.
Time frame: 6 weeks for each cohort.
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.
Dose limiting toxicity (DLT)
Time frame: 6 weeks.
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).
11 secondary outcomes
AUC
Time frame: 4 weeks
Cmax
Time frame: 4 weeks
Volume of distribution (Vd)
Time frame: 4 weeks
Plasma half-life of PDM08 (T ½)
Time frame: 4 weeks
Changes in tumour size by Computed Tomography (CT)
Time frame: 6 weeks
Tumour activity: Positron emission tomography (PET)
Time frame: 6 weeks
Myeloid cells in peripheral blood.
Time frame: 6 weeks
B and T lymphocytes and NK cells Populations
Time frame: 6 weeks
Serum Immunoglobulins
Time frame: 6 weeks
Complement components: C3 and C4; and C-Reactive Protein (CRP)
Time frame: 6 weeks
Serum cytokines
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge Barriuso, MD, PhD principal investigator
Hospital Universitario La Paz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PDM08 in people with Malignant Solid Tumours, run by Prodimed S.A. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and grade of adverse events by participant related to PDM08. (time frame: 6 weeks for each cohort.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2013.