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Phase 2 Study of Thermodox as Adjuvant Therapy With Thermal Ablation (RFA) in Treatment of Metastatic Colorectal Cancer(mCRC) (ABLATE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01464593
Recruitment Status : Terminated (trial design contingent on RFA optimization)
First Posted : November 3, 2011
Last Update Posted : March 7, 2016
Information provided by (Responsible Party):

Brief 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).

Condition or disease Intervention/treatment Phase
Colon Cancer Liver Metastasis Drug: Lyso-Thermosensitive Liposomal Doxorubicin Other: 5% Dextrose Solution Drug: ThermoDox Phase 2

Detailed Description:

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 reactions.

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 assessor.

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Open Label Trial of Thermal Ablation and Lyso-Thermosensitive Liposomal Doxorubicin (Thermodox) for Metastatic Colorectal Cancer (mCRC) Liver Lesions
Study Start Date : September 2011
Actual Primary Completion Date : May 2013
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Thermodox
Thermodox 50 mg/m2 intravenous infusion over 30 minutes starting 15 minutes before thermal ablation.
Drug: Lyso-Thermosensitive Liposomal Doxorubicin
Thermally sensitive liposomal doxorubicin 50 mg/m2 single 30 minute intravenous infusion.
Other Names:
  • Liposomal doxorubicin
  • Doxorubicin
  • Thermdox

Other: 5% Dextrose Solution
Single 30 minute intravenous infusion

Drug: ThermoDox
ThermoDox is a Lyso-thermosensitive Liposomal Doxorubicin designed to be used in conjunction with thermal ablation.

Primary Outcome Measures :
  1. Determine the local tumor control at 1 year post randomization [ Time Frame: 1 year ]
    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.

Secondary Outcome Measures :
  1. Evaluation of Safety [ Time Frame: 1 month ]
    Adverse events will be assessed through 1 month following study treatment(s). AE's after 1 month through the Month 25 assessment are reported if possibly, probably, or definitely related to study drug. Safety data will include physical exams, vital signs, ECGs, Echocardiograms/MUGA Scans, hematology, clinical chemistry and urinalysis.

  2. Time to Local Recurrence [ Time Frame: 2 years ]
    Measured as the time to local recurrence after ablation as measured from the date of randomization.

  3. Overall Survival [ Time Frame: 3 years ]
    Measured as time from randomization to death or the end of the study at month 37.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01464593

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United States, California
Los Angeles, California, United States, 90095
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Ohio
Cleveland Clinic Hospital
Cleveland, Ohio, United States, 44195
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
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Study Director: Nicholas Borys, M.D. Celsion
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Responsible Party: Celsion Identifier: NCT01464593    
Other Study ID Numbers: 104-10-201
First Posted: November 3, 2011    Key Record Dates
Last Update Posted: March 7, 2016
Last Verified: March 2016
Keywords provided by Celsion:
Colorectal Liver Metastasis
Colon Cancer
Liver Cancer
Liver Metastasis
Liver metastases
Additional relevant MeSH terms:
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Neoplasm Metastasis
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Neoplastic Processes
Pathologic Processes
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action