Phase I, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM14 Administered Intravenously to Patients with Advanced Solid Tumors
Overview
- Phase
- Phase 1/2
- Intervention
- PM14
- Conditions
- Not specified
- Sponsor
- Pharma Mar S.A.
- Enrollment
- 115
- Locations
- 7
- Primary Endpoint
- Patients with dose limiting toxicities
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Despite recent advances in the treatment of solid tumors in general, advanced (metastatic) disease remains mostly incurable and there is an urgent need to develop new therapeutic options for these patients, particularly investigational drugs with novel mechanisms of action. The investigation of new combination regimens of non-crossresistant agents with acceptable-and not completely overlapping-toxicities has been a major way to improve response rate and outcome of patients with advanced solid tumors.
Detailed Description
First-in-human, open-label, dose-finding, phase I trial, using a classical 3+3 design followed by a continual reassessment method (CRM). Patients will be included in cohorts of a minimum of three or six patients to receive PM14 at successively increasing dose levels, starting at 0.25 mg/m\^2 for the Days 1 and 8 schedule. For the Day 1 schedule, the starting dose will be 4.5 mg/m\^2. Dose escalation will proceed only after all the patients fully evaluable for DLT included at one dose level have completed the first cycle (i.e., three weeks). Once the RD has been determined, expansion cohorts will be included to have a minimum of 20 fully evaluable patients per indication (tumor type) treated in the Expansion phase (regardless of the schedule administered), and thus have an adequate number of patients to assess safety. The indications of these patients will be chosen depending on the efficacy data obtained during dose escalation. Patients treated at the expansion cohorts will be evaluable by the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) and/or by serum markers only in patients with prostate cancer (prostate specific-antigen \[PSA\]) or ovarian cancer (carbohydrate antigen-125 \[CA-125\]) according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively.
Investigators
Clinical Development Oncology Unit
Scientific
Pharma Mar S.A.
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
PM14
Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.
Intervention: PM14
Outcomes
Primary Outcomes
Patients with dose limiting toxicities
Time Frame: At cycle 2 (21-days cycle)
To identify the dose limiting toxicities (DLTs), and to determine the maximun tolerated dose (MTD) and the recommended dose (RD) of PM14 administered i.v. on two days (Day 1 and Day 8) or on Day 1 only, both every three weeks (q3wk) over three hours to patients with advanced solid tumors.
Overall response rate
Time Frame: Through study completion up to Cycle 9
To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.
Secondary Outcomes
- Clinical Benefit Rate(Through study completion up to Cycle 9)
- Pharmacokinetic: Maximum Plasma Concentration (Cmax)(At the end of Cycle 1 (each cycle is 21 days))
- Pharmacogenomic: Number of patients with RNA/protein expression(At the end of Cycle 1 (each cycle is 21 days))
- Progression-free Survival(From the date of first infusion of study treatment to the date of first documented progression or date of death from any cause, assessed up to 72 months)
- Duration of Response(From the date of the first documentation of response to the date of first PD or further therapy or death, assessed up to 72 months)
- Incidence of Treatment-Emergent Adverse Events(From the date of first infusion of study treatment to the date of study termination, assessed up to 72 months)
- Pharmacogenetic(At the end of Cycle 1 (each cycle is 21 days))
- Pharmacogenomic: Number of patients with Polymorphisms(At the end of Cycle 1 (each cycle is 21 days))
- Pharmacokinetic: Area Under The Concentration-time Curve (AUC)(At the end of Cycle 1 (each cycle is 21 days))
- Pharmacogenomic: Number of patients with Mutations(At the end of Cycle 1 (each cycle is 21 days))