Clinical Trial of PM60184 in Advanced Colorectal Cancer After Standard Treatment

INCLUSION CRITERIA:

1. Voluntarily written informed consent, obtained before the beginning of any study-specific procedures.
2. Age ≥ 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, regression 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).

   1. Adjuvant chemotherapy-based treatments count as prior therapy, as long as relapse had occurred during or within six months of completion of such therapies.
   2. Cumulative dose of prior oxaliplatin (if any) must be known.
   3. 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 \[first dose administration\]):

   1. At least three weeks since the last administration of an antineoplastic treatment (chemotherapy, biological, targeted or investigational therapies).
   2. 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.
   3. 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 ≥ 3 months.
10. Adequate bone marrow, liver, and kidney function:

    1. Hemoglobin ≥ 9 g/dL.
    2. Absolute neutrophil count ≥ 1.5 × 109/L.
    3. Platelet count ≥ 100 × 109/L.
    4. Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula).
    5. Albumin ≥ 2.5 g/dL.
    6. Total serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), except in case of Gilbert syndrome.
    7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5.0 × ULN in the case of liver metastases).
11. Recovery to grade ≤ 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 standards).
13. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure during the trial and up to six months after treatment discontinuation, and fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and up to four months after treatment discontinuation.

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):

   1. 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.
   2. Symptomatic cerebral and/or leptomeningeal metastasis, spinal cord compression or carcinomatous meningitis.
   3. Neuropathy of any etiology (other than that caused by previous antineoplastic therapy).
   4. 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 \[WHO\]).
   5. History of significant psychiatric disease.
   6. 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.
   7. Known active liver (hepatitis B or C or cirrhosis) or renal disease.
   8. Known human immunodeficiency virus (HIV) infection.
   9. Any other concomitant pathology that could jeopardize the patient's safety or commitment to complete the clinical trial.
   10. Inability or refusal to comply with the protocol or with the clinical trial procedures.
5. Pregnancy or lactation.