Advanced Colorectal Cancer MedDRA version: 20.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: PM60184
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: Not Applicable
CAS Number:
Sponsors
Pharma Mar, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Voluntarily written informed consent, obtained before the beginning of any study-specific procedures. 2) Age > or = 18 years. 3) Histologically-cytologically documented adenocarcinoma of colon or rectum that has progressed to the last prior treatment before inclusion. 4) Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. If the only tumor lesion is situated in a previously irradiated area or in an area subjected to other loco-regional therapy, progression in the lesion must be demonstrated radiologically. 5) Previous treatment in any setting with fluoropyrimidine, oxaliplatin and irinotecan in any combination (unless any is contraindicated). a) Adjuvant chemotherapy-based treatments count as prior therapy, as long as relapse had occurred during or within six months of completion of such therapies. b) Cumulative dose of prior oxaliplatin (if any) must be known. c) Prior cetuximab, panitumumab, bevacizumab, aflibercept, and regorafenib are allowed. 6) No more than two prior therapies for metastatic disease. 7) Washout periods for prior therapies (defined in relation to planned start of study treatment [first dose administration]): a) At least three weeks since the last administration of an antineoplastic treatment (chemotherapy, biological, targeted or investigational therapies). b) At least three weeks since radiotherapy involving up to 35% of bone marrow (radiotherapy involving > 35% of bone marrow is not allowed) or two weeks since the end of palliative radiotherapy including single doses. c) At least four weeks since any major surgical procedure, open biopsy, or significant traumatic injury. 8) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 9) Life expectancy > or = 3 months. 10)Adequate bone marrow, liver, and kidney function: a) Hemoglobin > or = 9 g/dL. b) Absolute neutrophil count > or =1.5 × 10 9/L. c) Platelet count > or = 100 × 10 9/L. d) Serum creatinine or = 40 mL/min (Cockcroft-Gault formula). e) Albumin > or = 2.5 g/dL. f) Total serum bilirubin < or = 1.5 times the upper limit of normal (ULN), except in case of Gilbert syndrome. g) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 × ULN (< or = 5.0 × ULN in the case of liver metastases). 11)Recovery to grade < or = 1 from any toxicity due to previous therapy (including peripheral sensory/motor neuropathy but excluding alopecia). 12)Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional sta
Exclusion criteria
Exclusion criteria: 1) Prior exposure to PM060184. 2) Known hypersensitivity to the study drug class or study drug excipient in the formulation. 3) Patients with locally advanced disease amenable to local and/or curative therapy (surgery or radiotherapy) at study entry. 4) Other serious and/or relevant diseases or clinical situations that, in the opinion of the Investigator, are incompatible with the protocol (including any of the following): a) History of another neoplastic disease (except for basal cell carcinoma of the skin, superficial bladder tumors, or properly treated carcinoma in situ of the uterine cervix or melanoma in situ) unless in remission for at least five years and with no recurrence. b) Symptomatic cerebral and/or leptomeningeal metastasis, spinal cord compression or carcinomatous meningitis. c) Neuropathy of any etiology (other than that caused by previous antineoplastic therapy). d) History of cardiac disease, such as myocardial infarction, in the year prior to registration in the clinical trial; symptomatic/uncontrolled angina pectoris; congestive heart failure or uncontrolled cardiac ischemia; any type of uncontrolled arrhythmia, congenital and/or prolonged QT interval or abnormal LVEF, or uncontrolled arterial hypertension (according to the standards of the World Health Organization [WHO]). e) History of significant psychiatric disease. f) Active infection requiring antibiotic, antifungal or antiviral treatment that, in the opinion of the Investigator, could compromise the patient’s capacity to tolerate the therapy. g) Known active liver (hepatitis B or C or cirrhosis) or renal disease. h) Known human immunodeficiency virus (HIV) infection. i) Any other concomitant pathology that could jeopardize the patient’s safety or commitment to complete the clinical trial. j) Inability or refusal to comply with the protocol or with the clinical trial procedures. 5) Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of PM060184 in terms of progression-free survival at 12 weeks (PFS3) in patients with advanced colorectal carcinoma (CRC) after standard therapy. ; Secondary Objective: -To evaluate OS, PFS, ORR, and d DOR. -To characterize the safety profile and feasibility of PM060184 in this population. -To describe peripheral neuropathy (PN) and QoL profiles in this population using patient-reported outcomes as measured by the EORTC QoL questionnaires for chemotherapy-induced peripheral neuropathy (QLQCIP20) and general QoL ( QLQ-C30). -To characterize the PK of PM060184 in this population. - To characterize the metabolomics of PM060184/biomarkers of PK, safety and/or efficacy response to PM060184. -To characterize pharmacogenetics of PM060184 in this population by identifying the presence or absence of germline mutations or polymorphisms that may help explain individual variability in the main PK parameters and safety outcomes. -To characterize pharmacogenomics of PM060184 in this population by analyzing the potential predictive factors (including BRAF-mutant-like gene expression subtypes) of sensitivity/resistance to PM060184 treatment ; Primary end point(s): PFS3, defined as the percentage of patients remaining alive and progression-free at Week 12 (Month 3) after the first treatment dose. ;Timepoint(s) of evaluation of this end point: Along the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Along the study; Secondary end point(s): -Overall survival (OS), defined as the time from the first day of treatment to the date of death or last contact. - Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation. - Overall response rate (ORR), defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.1. -Duration of response (DOR), defined as the time between the date when response criteria (PR or CR, the first to be reached) are fulfilled and the first date when PD, recurrence or death is objectively documented. -Treatment safety, including AEs, SAEs and laboratory abnormalities graded according to NCI-CTCAE v.4. Dose reductions or delays due to treatment-related AEs, and reasons for treatment discontinuations will also be analyzed. -PN and QoL profiles as reported by patients using the EORTC QLQ-CIPN20 and QLQ-C30. - PK parameters will be evaluated in plasma by population PK modeling and/or non-compartmental analysis. - Metabolomics of PM060184, i.e., intra- and interpatient systemic variations in the patient’s pre- and post-treatment metabolic profile. - PGt of PM060184 will be evaluated to identify the presence or absence of germline mutations or polymorphisms that may help explain individual variability in the main PK parameters and safety outcomes. - PGx of PM060184 will be evaluated to determine predictive/prognostic markers of response and/or resistance to PM060184. | — |
Countries
Belgium, Canada, Spain, United States
Contacts
Public ContactClinical Trials
Pharma Mar, S.A.
Outcome results
None listed