- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01464593
Phase 2 Study of Thermodox as Adjuvant Therapy With Thermal Ablation (RFA) in Treatment of Metastatic Colorectal Cancer(mCRC) (ABLATE)
Phase II Open Label Trial of Thermal Ablation and Lyso-Thermosensitive Liposomal Doxorubicin (Thermodox) for Metastatic Colorectal Cancer (mCRC) Liver Lesions
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA
-
-
New York
-
Bronx, New York, United States, 10467
- Montefiore Medical Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Hospital
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Pathologic diagnosis of colorectal cancer.
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.
- 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.
- Male or female 18 years of age or older.
- Are willing to sign an informed consent form.
- Left Ventricular Ejection Fraction(LVEF) ≥ 50%
- Willing to return to the study site for study visits.
- Have ECOG performance status ≤ 2 and life expectancy of ≥ 6 months.
Exclusion Criteria:
- Concomitant bowel surgery and/or synchronous colon resection.
- 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.
- Have previously received any doxorubicin (study subjects being considered for completion of treatment may have received ThermoDox previously).
- Are pregnant or breast-feeding. In women of childbearing potential, a negative pregnancy test (serum) is required within 14 days prior to study treatment.
- 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.
- Have any known allergic reactions to any of the drugs or liposomal components or intravenous imaging agents to be used in this study.
- Have portal or hepatic vein tumor invasion/thrombosis.
- 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.
- 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).
- Have serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤ 25.0 mL/min.
- Have serum bilirubin > 3.0 mg/dL.
- Have serum albumin < 2.8 g/dL.
- Have body temperature > 38.3°C immediately prior to study treatment.
- Have contraindications to receiving doxorubicin HCl.
- 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.
- 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).
- 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.
- Documented HIV positive.
- NYHA class III or IV functional classification for heart failure.
- Evidence of hemochromatosis.
- Have history of contrast induced nephropathy and unable to undergo MRI.
- Have a history of Nephrogenic Systemic Fibrosis (NSF).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Thermodox
Thermodox 50 mg/m2 intravenous infusion over 30 minutes starting 15 minutes before thermal ablation.
|
Thermally sensitive liposomal doxorubicin 50 mg/m2 single 30 minute intravenous infusion.
Other Names:
Single 30 minute intravenous infusion
ThermoDox is a Lyso-thermosensitive Liposomal Doxorubicin designed to be used in conjunction with thermal ablation.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 month
|
Time to Local Recurrence
Time Frame: 2 years
|
Measured as the time to local recurrence after ablation as measured from the date of randomization.
|
2 years
|
Overall Survival
Time Frame: 3 years
|
Measured as time from randomization to death or the end of the study at month 37.
|
3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Nicholas Borys, M.D., Imunon
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Neoplastic Processes
- Colorectal Neoplasms
- Neoplasm Metastasis
- Colonic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
- 104-10-201
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colon Cancer Liver Metastasis
-
Memorial Sloan Kettering Cancer CenterRecruitingColorectal Cancer | Colon Cancer | Liver Metastasis Colon Cancer | Adenocarcinoma of the Rectum | Colon Cancer Liver Metastasis | Adenocarcinoma of the ColonUnited States
-
McGill University Health Centre/Research Institute...RecruitingLiver Dysfunction | Liver Metastasis Colon Cancer | Liver RegenerationCanada
-
Lawson Health Research InstituteBayerRecruiting
-
AllVascularRecruitingLiver Metastasis Colon CancerAustralia
-
University of ManchesterManchester University NHS Foundation Trust; The Christie NHS Foundation Trust; Perspect... and other collaboratorsUnknownCancer | Colorectal Cancer | Liver Metastasis Colon Cancer | Cancer MetastaticUnited Kingdom
-
First Affiliated Hospital, Sun Yat-Sen UniversityNot yet recruitingLiver Metastasis Colon CancerChina
-
University of LeedsNational Cancer Institute (NCI); Massachusetts General Hospital; Massachusetts... and other collaboratorsRecruitingColon Cancer Liver MetastasisUnited Kingdom
-
Western University, CanadaNot yet recruitingNAFLD | Liver Metastasis Colon Cancer | Liver Steatoses
-
International Group of Endovascular OncologyCompletedObservational Study on Second Line Treatment of Liver Metastases With DEBIRI and Cetuximab (TACETUX)Colon Cancer Liver MetastasisItaly
-
PerspectumActive, not recruitingLiver Cancer | Liver Metastasis Colon CancerUnited Kingdom
Clinical Trials on Lyso-Thermosensitive Liposomal Doxorubicin
-
National Institutes of Health Clinical Center (CC)National Cancer Institute (NCI)CompletedMetastatic Cancer | Liver CancerUnited States, China
-
Duke UniversityNational Cancer Institute (NCI)Terminated
-
Children's National Research InstituteRecruitingSoft Tissue Sarcoma | Ewing Sarcoma | Bone Metastases | Solid Tumors | Rhabdomyosarcoma | Wilms Tumor | Germ Cell Tumor | Hepatic Tumor | Malignant Epithelial NeoplasmUnited States
-
AeRang KimTerminatedOsteosarcoma | Ewing Sarcoma | Neuroblastoma | Solid Tumors | Pediatric Cancer | Rhabdomyosarcoma | Wilms Tumor | Soft Tissue Sarcomas | Germ Cell Tumors | Hepatic TumorUnited States
-
UMC UtrechtCenter for Translational Molecular Medicine; Dutch Cancer Society; Vrienden UMC...RecruitingBreast Cancer | Breast Neoplasms | Metastatic Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Invasive Ductal Breast Cancer | Invasive Ductal Carcinoma of Female Breast | Adenocarcinoma BreastNetherlands
-
University of OxfordOxford University Hospitals NHS Trust; ImunonCompletedLiver TumourUnited Kingdom
-
National Cancer Institute (NCI)CompletedDS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | Male Breast Carcinoma | Stage IV Breast Cancer AJCC...United States
-
ARCAGY/ GINECO GROUPCompletedOvarian CancerFrance
-
Azaya Therapeutics, Inc.UnknownCancer | Ovarian Cancer | Ovarian Epithelial Cancer Recurrent | Malignant Female Reproductive System Neoplasm | Ovarian TumorCanada, United States