A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47
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|ClinicalTrials.gov Identifier: NCT02340208|
Recruitment Status : Active, not recruiting
First Posted : January 16, 2015
Last Update Posted : August 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer||Drug: L-DOS47||Phase 1 Phase 2|
Patients will be recruited into cohorts, with a minimum of three and a maximum of six patients per cohort. All patients at a given dose level must complete Cycle 1 (3 week period) before escalation in subsequent patients can proceed. The decision for dose escalation to the next dose level will be made after the safety and available pharmacokinetic (PK) data have been reviewed by the Trial Steering Committee (TSC).
Escalation of L-DOS47 will continue until a maximum tolerated dose (MTD) is reached.
After the MTD of L-DOS47 has been determined in Phase I, up to 20 patients will be enrolled (taken forward from Phase I) to evaluate the preliminary efficacy of L-DOS47 (i.e., response rate using the Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1 criteria, disease progression and survival); monitoring will include radiologic evaluations every second cycle. The safety and tolerability of L-DOS47 will also be further evaluated. Pharmacokinetic information will be collected as well as relevant observations on the activity of L-DOS47.
For all patients, treatment with L-DOS47 will continue either until the patient experiences disease progression, unacceptable toxicity, the patient withdraws consent or has completed four treatment cycles and does not wish to continue with additional cycles, whichever occurs first. After four cycles, patients may continue to receive L-DOS47 for as long as there is sustained clinical benefit and it is well tolerated, in the opinion of the Investigator.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||76 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients|
|Study Start Date :||May 2012|
|Estimated Primary Completion Date :||October 2017|
|Estimated Study Completion Date :||December 2017|
Patient will be recruited into cohorts of L-DOS47 escalating doses, with a minimum of 3 and a maximum of 6 patients per cohort. The starting dose of L-DOS47 will be 0.12 μg/kg; further possible dose levels include 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45, 3.26 and 4.33 μg/kg.
A treatment cycle will be 21 days with patients receiving L-DOS47 on cycle Days 1 and 8.
- The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47 [ Time Frame: Up to 12 weeks ]Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
- L-DOS47 related toxicity during the first 2 hours after infusion [ Time Frame: During the first 2 hours after infusion ]Assessed by the incidence and severity of AEs and SAEs and changes in vital signs
- The incidence and severity of all reported adverse events and serious adverse events [ Time Frame: Participants will be followed for 12 weeks and the 30 day follow-up period ]Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.
- Changes from baseline for additional safety parameters (clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG) [ Time Frame: Up to 12 weeks ]Safety parameters include clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG
- The evaluation of anti-L-DOS47 antibody over time [ Time Frame: Up to 12 weeks ]Serum samples will be collected and analyzed from all patients dosed with L-DOS47.
- Maximum observed plasma concentration (Cmax) of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
- Time to maximum observed plasma concentration (Tmax) of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
- Area under the concentration (AUC) vs time curve of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.
- Terminal elimination half-life of L-DOS47 at each dose level [ Time Frame: Up to 12 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02340208
|Mazovian Center of Pulmonary Diseases and Tuberculosis|
|Med. Polonia Hospital Poznan|
|Institute of Tuberculosis and Lung Diseases|
|Military Medical Institute|
|The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology|
|Principal Investigator:||Dariusz Kowalski, MD, PhD||The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology|