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Phase II Open Label Trial of Thermal Ablation and Lyso-Thermosensitive Liposomal Doxorubicin (Thermodox) for Metastatic Colorectal Cancer (mCRC) Liver Lesions

Phase 2
18 Years
Not Enrolling
Colon Cancer Liver Metastasis

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Trial Information

Phase II Open Label Trial of Thermal Ablation and Lyso-Thermosensitive Liposomal Doxorubicin (Thermodox) for Metastatic Colorectal Cancer (mCRC) Liver Lesions

This is an open label phase II trial to evaluate the safety, feasibility, and efficacy of
ThermoDox in combination wtih thermal ablation for the regional hepatic treatment of mCRC
liver lesions.

Eligible colorectal cancer patients will unresectable liver metastases and be candidate for
either radiofrequency ablation (RFA) or microwave ablation (MWA). All unresectable lesions
must be targeted for ablation in in nor more than 2 thermal ablation/ThermoDox procedures.

Approximately 24 hours prior to treatment with ThermoDox, patients will start a regimen of
prophylaxis (detailed in the Study Drug section below) against immediate hypersensitivity

Treatment will begin with a 50 mg/m2 ThermoDox infusion administered intravenously (IV) over
30 minutes. Thermal Ablation will be initiated a minimum of 15 minutes after start of the
infusion and should be completed no later than 3 hours after starting the infusion. Subjects
will have follow up visits on Day 14 and at months 1, 4, 7, 10,13, 16, 19, 22, and 25 (+ 7
days) or until study discontinuation.

At baseline and at each post-treatment clinic visit, patients will self-report their
"quality of life" (QoL) using the 8-item FACT-Hepatobiliary Symptom Index (FHSI-8).

Contrast CT imaging studies or Magnetic Resonance Imaging (MRI)will be used to assess the
effectiveness of therapy. CT or MRI scans will be obtained at baseline and at months 1, 4,
7, 10, 13, 16, 19, 22, and 25(+ 7 days)until local recurrence is seen, the subject has
discontinued, or 2 years of follow-up have elapsed, whichever occurs first. All
protocol-specified CT/MRI images will be centrally read by an independent radiology

Subjects will be followed for each efficacy endpoint local tumor control through 2 years
after treatment. Secondary endpoints including Overall Survival, Time to Local Recurrence,
PRO deterioration) will be evaluated until the event occurs, the subject is discontinued, or
until 3 years following treatment.

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

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

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).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the local tumor control at 1 year post randomization

Outcome Description:

Subject's treated with thermal ablation in conjunction with Thermodox to evaluate local tumor control defined as complete ablation and does not experience recurrence within 1 cm of the ablation site.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Nicholas Borys, M.D.

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

June 2013

Related Keywords:

  • Colon Cancer Liver Metastasis
  • Colorectal Liver Metastasis
  • Colon Cancer
  • Liver Cancer
  • Liver Metastasis
  • Liver metastases
  • Colonic Neoplasms
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Liver Neoplasms



Rhode Island Hospital Providence, Rhode Island  02903
Montefiore Medical Center Bronx, New York  10467-2490
UCLA Los Angeles, California  90095
Cleveland Clinic Hospital Cleveland, Ohio  44195