Study of PM01183 in Non-Colorectal Cancer Patients as a Days 1 and 8 Intravenous Short Infusion Every 3 Weeks

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 on Days 1 and 8 Every Three Weeks (q3wk) in Non-Colorectal Cancer (Non-CRC) Patients

Phase I Study of PM01183 in Non-Colorectal Cancer Patients to determine the recommended dose (RD) of PM01183.

Study Overview

• Status: Completed
• Conditions: Major Advanced Solid Tumors Other Than Colorectal
• Intervention / Treatment: Drug: PM01183

Detailed Description

Phase I Study of PM01183 in Non-Colorectal (non-CRC) Cancer Patients to determine the recommended dose (RD) of PM01183, to characterize the safety profile, compliance and feasibility of the schedule, to optimize and individualize PM01183 dosing in non-CRC patients according to individual tolerance, to characterize the pharmacokinetics (PK) of the schedule, to obtain preliminary information on the clinical antitumor activity and to perform an exploratory pharmacogenomics (PGx) analysis.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Cancer Research Center. University of Chicago Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntarily signed and dated written informed consent
2. Age ≥ 18 years.
3. Non or minimally daily activities-interfering disease related symptoms.
4. Life expectancy ≥ 3 months.
5. Patients with solid tumor other than CRC.
6. Adequate bone marrow, renal, hepatic, and metabolic function (tests within normal limits or only minimally altered as assessed ≤ 7 days before inclusion in the study)Recovery to asymptomatic or minimally altered or to baseline from any adverse event (AE) derived from previous treatment (mild alteration for alopecia, skin toxicity or fatigue are allowed).
7. Normal cardiac function cardiac function by appropriate image testing.
8. Women of childbearing potential must have a negative serum pregnancy test before study entry.

Exclusion Criteria:

1. Primary colorectal cancer diagnosis
2. Prior treatment with PM01183.

3. Concomitant diseases/conditions:

   a) History of a clinically relevant cardiac condition c) Known chronic liver disease. d) Active uncontrolled infection. e) Known human immunodeficiency virus (HIV) infection. f) Limitation of the patient's ability to comply with the treatment or follow-up protocol.

4. Symptomatic and progressive or corticosteroid-requiring documented brain metastases
5. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
6. History of extensive prior pelvic irradiation.
7. History of previous bone marrow and/or stem cell transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: A; Patients will receive PM01183 on Days 1 and 8 q3wk (three weeks = one treatment cycle) as an i.v. infusion, starting at 3.0 mg/day, flat dose (FD), over a minimum total volume of 100 ml dilution (on 5% glucose or 0.9% sodium chloride) via a central catheter or over a minimum total volume of 250 ml via a peripheral line, over one hour (at a fixed rate) and through a pump device.

Drug: PM01183; PM01183 drug product (DP) is presented as a lyophilized powder for concentrate for solution for infusion with two strengths, 1 mg and 4 mg vials. Before use, the 1 mg and 4 mg vials should be reconstituted with 2 ml and 8 ml of water for injection respectively, to give a solution containing 0.5 mg/ml PM01183. For administration to patients as an i.v. infusion, reconstituted vials are diluted with glucose 50 mg/ml (5%) solution for infusion or sodium chloride 9 mg/ml (0.9%) solution for infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended dose (RD)	To determine the recommended dose (RD) of PM01183 administered as a 1-hour infusion intravenously (i.v.) on Days 1 and 8 every three weeks (q3wk) in non-colorectal cancer (non-CRC) patients.	From treatment onset to end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): The dose-exposure relationships for Cmax and area under the curve (AUC) will be evaluated.	To characterize the pharmacokinetics (PK) of this schedule and explore factors that may affect individual variability in main PK parameters.	During the infusions administered on Day 1 of Cycles 1 and 3, with a schedule of 13 samples.
Antitumor activity measured clinically and/or radiologically according to RECIST or by evaluation of tumor markers	RECIST (Response Evaluation Criteria In Solid Tumors) is a set of published rules that define when cancer patients improve ("respond"), stay the same ("stable") or worsen ("progression") during treatments.	Every six weeks while on treatment. Patients who discontinued treatment without disease progression will be followed every three months until disease progression, other antitumor therapy, death or until the end-of-study date, whichever occurs first.
Pharmacogenomics (PGx) analysis: Number of tumour patient samples with identified and validated putative molecular markers associated with the clinical outcome of non-CRC patients treated with PM01183.		At the end of the study (24 months)

Collaborators and Investigators

• Sponsor: PharmaMar

Publications and helpful links

General Publications

• Fernandez-Teruel C, Lubomirov R, Fudio S. Population Pharmacokinetic-Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin. J Clin Pharmacol. 2021 Sep;61(9):1206-1219. doi: 10.1002/jcph.1886. Epub 2021 Jun 9.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: July 26, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): January 15, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Pharma Mar; PM01183; Non-Colorectal Cancer (non-CRC); Dose finding phase I
• Other Study ID Numbers: PM1183-A-005-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No