Clinical trial NCT01405391: Study of PM01183 in Non-Colorectal Cancer Patients as a Days 1 and 8 Intravenous Short Infusion Every 3 Weeks
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Advanced Solid Tumors Other Than Colorectal
Keywords: Pharma Mar
PM01183
Non-Colorectal Cancer (non-CRC)
Dose finding phase I
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 42
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: Phase I Study of PM01183 in Non-Colorectal Cancer Patients to determine the recommended dose (RD) of 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recommended dose (RD)
timeFrame: From treatment onset to end of treatment
Secondary outcomes:
measure: Pharmacokinetics (PK): The dose-exposure relationships for Cmax and area under the curve (AUC) will be evaluated.
timeFrame: During the infusions administered on Day 1 of Cycles 1 and 3, with a schedule of 13 samples.
measure: Antitumor activity measured clinically and/or radiologically according to RECIST or by evaluation of tumor markers
timeFrame: 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.
measure: 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.
timeFrame: At the end of the study (24 months)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Chicago
country: United States
facility: Cancer Research Center. University of Chicago Hospitals
state: Illinois
Study officials:
References:
citation: 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.