A Dose Escalation Study of LNA-i-Mir-221 for Cancer Treatment

Inclusion Criteria:

* Men and women age ≥18 yrs
* Diagnosis of symptomatic multiple myeloma with measurable disease, i.e. detectable monoclonal component (MC) in the serum and/or urine.
* Patients with evidence of refractory disease according to IMWG criteria, who are either not suitable for bone marrow transplantation procedures or have relapsed after bone marrow transplantation and have failed at least three prior lines of therapy (10) (i.e. patients with lack of response or patients whose disease progresses on or within 60 days after the completion of last treatment).
* Histologically diagnosed stromal or epithelial solid tumors (clinically diagnosed HCC according to AASLD/EASLD guidelines).
* Patients with inoperable tumor(s) and no applicable curative therapy, not amenable to loco-regional therapy and/or codified standard systemic treatment, as established in the context of internationally accepted treatment guidelines for the various types of tumors that will be enrolled. One measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Life expectancy of at least three months according to physician evaluation
* ECOG 0-2
* Screening hematology, clinical chemistries, coagulation and urine analyses are not clinically significant and the following criteria are met:

  1. Platelets \>75,000/mm3
  2. ANC \>1000/mm3
  3. Hemoglobin \> 8 g/dL
  4. Total and direct bilirubin \< 2.5 mg/dl (except for clearly documented Gilbert's Syndrome)
  5. ALT and AST \< 5 x ULN
  6. International normalized ratio (INR) \<2.3 or prothrombin time (PT) \<6 seconds above control
  7. Serum creatinine WNL and estimated by the Cockcroft-Gault formula or measured creatinine clearance rate \> 40 ml/min
* Negative results on the following screening laboratory tests:

  1. urine or serum pregnancy test (for women of childbearing potential),
  2. human immunodeficiency virus (HIV) antibody.
* For men and women of childbearing potential, willingness to utilize adequate contraception and not become pregnant (or have their partner become pregnant) during the full course of the study.
* For female study participants, adequate birth control methods will be defined as: intrauterine device or double barrier contraception, i.e., condom plus diaphragm, condom or diaphragm plus spermicidal gel /foam
* For males study participants, adequate birth control methods will be defined as:

double barrier contraception, i.e., condom plus diaphragm; condom or diaphragm plus spermicidal gel/foam.

Note: Females who are not of childbearing potential must meet one of the following criteria:

1. Post-menopause - defined as one year without menses or follicle-stimulating hormone (FSH) of \>40 U/mL
2. Surgical menopause - hysterectomy, bilateral oophorectomy, or bilateral tubal ligation
3. Pregnancy, breastfeeding

   * Subjects who participated to any other investigational drug trial within 30 days before enrollment to this trial
   * Severe liver dysfunction (Child-Pugh Class C or hepatic encephalopathy).
   * Serious medical or psychiatric illness, that may affect the correct participation to the trial
   * Concurrent social conditions (e.g. drug/alcohol abuse issue), that would potentially affect the correct participation to the trial New York Heart Association (NYHA) Class III or IV
   * cardiac disease, myocardial infarction within the past 6 months, unstable and/or symptomatic arrhythmia, or evidence of ischemia on ECG
   * Patients with active infections requiring systemic therapy are ineligible
   * Patients HIV positive or acquired immunodeficiency syndrome-related illness are ineligible
   * History of other malignancies within 3 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or breast, low grade, early stage localized prostate cancer treated surgically with curative intent (TNM stage of T1a or T1b)
   * Voluntary written informed consent released before any study related procedure is performed. The consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

* Pregnancy,
* breastfeeding
* Subjects who participated to any other investigational drug trial within 30 days before enrollment to this trial
* Severe liver dysfunction (Child-Pugh Class C or hepatic encephalopathy).
* Serious medical or psychiatric illness, that may affect the correct participation to the trial
* Concurrent social conditions (e.g. drug/alcohol abuse issue), that would potentially affect the correct participation to the trial New York Heart Association (NYHA) Class III or IV
* cardiac disease, myocardial infarction within the past 6 months, unstable and/or symptomatic arrhythmia, or evidence of ischemia on ECG
* Patients with active infections requiring systemic therapy are ineligible
* Patients HIV positive or acquired immunodeficiency syndrome-related illness are ineligible
* History of other malignancies within 3 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or breast, low grade, early stage localized prostate cancer treated surgically with curative intent (TNM stage of T1a or T1b)
* ECOG\>2