Clinical Trial of PM60184 in Advanced Colorectal Cancer After Standard Treatment
Condition: Advanced Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: PM060184
Intervention description: PM060184: 9.3 mg/m2 PM060184 i.v. as a 30-minute infusion via a central or peripheral venous catheter.Dose can be rounded to the first decimal point.
PM060184 will be administered on Day 1 and Day 8 q3wk. (Three weeks=one treatment cycle).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial will evaluate the efficacy of PM060184 in terms of progression-free survival at 12
      weeks (PFS3) in advanced or metastatic Colorectal Cancer (CRC) patients with any KRAS
      mutation status (wild- type; mutated; or unknown status) progressing after standard
      treatments (fluoropyrimidine, irinotecan, and oxaliplatin).

      Patients in this trial will receive PM060184 at a dose of 9.3 mg/m2 as a 30-minute
      intravenous (i.v.) infusion on Days 1 and 8 q3wk.
    

Eligibility criteria:

        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.