Phase 2 Study of Thermodox as Adjuvant Therapy With Thermal Ablation (RFA) in Treatment of Metastatic Colorectal Cancer(mCRC)
Condition: Colon Cancer Liver Metastasis
MeSH terms: Neoplasm Metastasis; Colonic Neoplasms
Intervention: Lyso-Thermosensitive Liposomal Doxorubicin; 5% Dextrose Solution; ThermoDox
Intervention description: Thermally sensitive liposomal doxorubicin 50 mg/m2 single 30 minute intravenous infusion.; Single 30 minute intravenous infusion; ThermoDox is a Lyso-thermosensitive Liposomal Doxorubicin designed to be used in conjunction with thermal ablation.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Liver Metastasis; Colon Cancer; Liver Cancer; Liver Metastasis; Liver metastases

Summary:

      The purpose of this study is to determine the safety and efficacy of Thermodox, a thermally
      sensitive liposomal doxorubicin, in combination with thermal ablation in the treatment of
      hepatic colorectal liver metastases (CRLM).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologic diagnosis of colorectal cancer.

          2. A minimum of 1 unresectable mCRC liver lesion at baseline clinically indicated for
             radiofrequency ablation (RFA) or microwave ablation (MWA).

               -  Recurrent lesions may have been treated previously by resection or ablation.

               -  Anticipated ablation volume will be no larger than either removal of 3 hepatic
                  segments or removal of more than 30% of total liver volume (as per maximum
                  surgical limit).

               -  Patients may have resectable lesions that are treated surgically.

               -  If additional lesions are discovered during the ablation treatment procedure that
                  were undetectable at screening will be treated at the discretion of the physician
                  and guided by local standard of care.

               -  Confirm the lesions are malignant by a pretreatment biopsy or by a biopsy
                  obtained during the ablation procedure.

          3. Subjects with suspected or limited extra-hepatic mCRC are eligible provided thermal
             ablation is clinically indicated. Chemotherapy is not permitted within 5 half-lives or
             30 days if shorter prior to initial study treatment through 30 days following final
             study treatment.

          4. Male or female 18 years of age or older.

          5. Are willing to sign an informed consent form.

          6. Left Ventricular Ejection Fraction(LVEF) ≥ 50%

          7. Willing to return to the study site for study visits.

          8. Have ECOG performance status ≤ 2 and life expectancy of ≥ 6 months.

        Exclusion Criteria:

          1. Concomitant bowel surgery and/or synchronous colon resection.

          2. Have serious illnesses including, but not limited to, congestive heart failure;life
             threatening cardiac arrhythmia; or myocardial infarction or cerebral vascular accident
             within the last 6 months.

          3. Have previously received any doxorubicin (study subjects being considered for
             completion of treatment may have received ThermoDox previously).

          4. Are pregnant or breast-feeding. In women of childbearing potential, a negative
             pregnancy test (serum) is required within 14 days prior to study treatment.

          5. Women and men of childbearing potential who are not practicing an acceptable form of
             birth control (i.e. diaphragm, cervical cap, condom, surgical sterility or birth
             control pills.

          6. Have any known allergic reactions to any of the drugs or liposomal components or
             intravenous imaging agents to be used in this study.

          7. Have portal or hepatic vein tumor invasion/thrombosis.

          8. Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjects
             who are therapeutically anticoagulated for medical conditions unrelated to CRLM such
             as atrial fibrillation. Subjects may be re-screened after condition is treated or
             anticoagulant is withheld.

          9. Have platelet count < 75,000/mm3, absolute neutrophil count < 1500/mm3, or Hgb < 10.0
             g/dL (unless the hemoglobin value has been stable, the subject is cardiovascularly
             stable, asymptomatic, and judged able to withstand the RFA procedure).

         10. Have serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤ 25.0
             mL/min.

         11. Have serum bilirubin > 3.0 mg/dL.

         12. Have serum albumin < 2.8 g/dL.

         13. Have body temperature > 38.3°C immediately prior to study treatment.

         14. Have contraindications to receiving doxorubicin HCl.

         15. Are being treated with other investigational agents or use of an investigational agent
             within 5 half-lives or 30 days whichever is longer preceding the first dose of study
             medication.

         16. Use of chemotherapy within 5 half-lives or 30 days, whichever is shorter, preceding
             the first dose of study medication and no chemotherapy planned for 30 days after
             ablation(s).

         17. Have concurrent malignancy other than mCRC (subjects wtih treated squamous cell
             carcinoma of the skin or basal cell carcinoma of the skin maybe included) or ongoing
             medically significant active infection.

         18. Documented HIV positive.

         19. NYHA class III or IV functional classification for heart failure.

         20. Evidence of hemochromatosis.

         21. Have history of contrast induced nephropathy and unable to undergo MRI.

         22. Have a history of Nephrogenic Systemic Fibrosis (NSF).