Phase 2 Study of Thermodox as Adjuvant Therapy With Thermal Ablation (RFA) in Treatment of Metastatic Colorectal Cancer(mCRC) (ABLATE)
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).
Colon Cancer Liver Metastasis
Drug: Lyso-Thermosensitive Liposomal Doxorubicin
Other: 5% Dextrose Solution
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- Determine the local tumor control at 1 year post randomization [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- Evaluation of Safety [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]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.
- Time to Local Recurrence [ Time Frame: 2 years ] [ Designated as safety issue: No ]Measured as the time to local recurrence after ablation as measured from the date of randomization.
- Overall Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]Measured as time from randomization to death or the end of the study at month 37.
|Study Start Date:||September 2011|
|Study Completion Date:||June 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
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:Other: 5% Dextrose Solution
Single 30 minute intravenous infusionDrug: ThermoDox
ThermoDox is a Lyso-thermosensitive Liposomal Doxorubicin designed to be used in conjunction with thermal ablation.
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.
|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|
|Study Director:||Nicholas Borys, M.D.||Celsion|