- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01888302
Sirolimus, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients At High Risk for Cholangiocarcinoma Recurrence After Liver Transplant or Surgery
Pilot Trial of Sirolimus, Gemcitabine and Cisplatin for Patients With High Risk for Cholangiocarcinoma Recurrence
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Assessment of the percentage of patients who are able to complete therapy through 4 and 6 months post-registration.
SECONDARY OBJECTIVES:
I. To describe the adverse events, rate of dose reductions, and quality of life in these patients.
II. To summarize timed endpoints of time-to-recurrence, disease-free survival, overall survival, time to treatment failure, and time until treatment related grade 3+ adverse events.
OUTLINE:
Patients receive cisplatin intravenously (IV) over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and sirolimus orally (PO) daily or three times weekly. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologic proof of presence of residual tumor in liver explants and /or positive resection margins
- Absolute neutrophil count (ANC) >= 1500/μL obtained =< 7 days prior to registration
- Platelets (PLT) >= 100,000/μL obtained =< 7 days prior to registration
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 7 days prior to registration
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN obtained =< 7 days prior to registration (=< 5 x ULN in patients with liver metastases)
- Creatinine =< 1.5 x Institutional ULN obtained =< 7 days prior to registration
- Alkaline phosphatase =< 5 x institutional ULN obtained =< 7 days prior to registration
- Hemoglobin (Hgb) >= 9.0 g/dL obtained =< 7 days prior to registration
- International normalized ratio (INR) and partial thromboplastin (PTT) =< 3.0 x ULN (anticoagulation is allowed if target INR =< 3.0 x ULN on a stable dose of warfarin or on a stable dose of low molecular weight [LMW] heparin for > 2 weeks at time of registration)
- Fasting serum glucose < 1.5 x ULN obtained =< 7 days prior to registration
- Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN obtained =< 90 days prior to registration; NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Ability to provide informed consent
- Willingness to return to Mayo Clinic for follow up
- Life expectancy >= 12 months
- Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration
- Four months post liver transplant
Exclusion Criteria:
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Clinically significant cardiac disease, especially history of myocardial infarction =< 6 months, or congestive heart failure (New York Heart Association [NYHA] classification III or IV) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Taking strong inhibitors or strong/moderate inducers of cytochrome P450 (CYP)3A4
Strong inhibitors of CYP3A4/5; > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance
- Clarithromycin (Biaxin®, Biaxin XL®)
- Conivaptan (Vaprisol®)
- Grapefruit juice
- Itraconazole (Sporanox®)
- Ketoconazole (Nizoral®)
- Mibefradil
- Nefazodone (Serzone®)
- Posaconazole (Noxafil®)
- Telaprevir (Incivek®)
- Telithromycin (Ketek®)
Use of the following inducers are prohibited =< 7 days prior to registration
Strong inducers of CYP3A4/5; > 80% decrease in AUC
- Avasimibe
- Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
- Phenytoin (Dilantin®, Phenytek®)
- Rifampin (Rifadin®)
- St. John's wort
Moderate inducers of CYP3A4/5; 50-80% decrease in AUC
- Bosentan (Tracleer®)
- Modafinil (Provigil®)
- Nafcillin
- Phenobarbital (Luminal®)
- Rifabutin (Mycobutin®)
- Troglitazone
Any of the following prior therapies:
- Chemotherapy =< 4 weeks prior to registration
- Mitomycin C/nitrosoureas =< 6 weeks prior to registration
- Immunotherapy =< 4 weeks prior to registration
- Biologic therapy =< 4 weeks prior to registration
- Radiation therapy =< 4 weeks prior to registration
- Radiation to > 25% of bone marrow prior to registration
- Failure to fully recover from acute, reversible effects of prior surgery or chemotherapy regardless of interval since last treatment
Any of the following because this study involves cytotoxic agents
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive with low cluster of differentiation (CD)4 count; Note: previous calcineurin inhibitor or previous sirolimus use allowed
- Current active other malignancy, except non-melanoma skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
- Current impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sirolimus (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Current severely impaired lung function (i.e., forced expiratory volume in 1 second [FEV1] < 1 liter)
- Received immunization with attenuated live vaccines =< 7 days prior to study entry or during study period; NOTE: Close contact with those who have received attenuated live vaccines should be avoided during treatment with sirolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella and typhoid (TY)21a typhoid vaccines
- Current severe hepatic impairment; Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (cisplatin, gemcitabine hydrochloride, sirolimus)
Patients receive cisplatin IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and sirolimus PO daily or three times weekly.
Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of patients who are able to complete therapy
Time Frame: Up to 6 months post-registration
|
Up to 6 months post-registration
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Steven Alberts, Mayo Clinic
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 (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Recurrence
- Cholangiocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Gemcitabine
- Cisplatin
- Sirolimus
Other Study ID Numbers
- MC1243 (OTHER: Mayo Clinic)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2013-01183 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- 12-007515
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 Hepatic Complication
-
Assiut UniversityUnknownHepatic Complication
-
Stefan Gilg, MD, PhDUnknownLiver Failure as A Complication of Care
-
Boris Gala LopezMcGill University Health Centre/Research Institute of the McGill University...WithdrawnLiver Failure as A Complication of Care | 30-day Mortality
-
University Hospital, LinkoepingRecruitingMRI | Liver Resection | Liver Failure as A Complication of CareSweden, Norway, Denmark, Finland
-
Huashan HospitalRecruiting
-
National Cancer Institute (NCI)Glaxosmithkline Biologicals S.A.TerminatedRenal Failure | Solid Neoplasm | BRAF Gene Mutation | Hepatic ComplicationUnited States, Canada
-
Ramsay Générale de SantéEuropean Clinical Trial Experts NetworkRecruitingIron Metabolism Disorders | Hemodialysis Complication | Calcium Phosphate Metabolism | Hepatic Metabolic DisordersFrance
-
Novartis PharmaceuticalsCompletedNormal Hepatic Function | Impaired Hepatic FunctionUnited States
-
Novartis PharmaceuticalsCompletedNormal Hepatic Function | Impaired Hepatic FunctionBelgium, Germany, Israel, Bulgaria, United States
-
Asst Melegnano e MartesanaEnrolling by invitationMortality | Nephrotoxicity | Respiratory Complication | Neurological Complication | Surgical Complication | Metabolic Complication | Cardiovascular ComplicationItaly
Clinical Trials on Quality-of-Life Assessment
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol Specific | Malignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)RecruitingChildhood Malignant NeoplasmUnited States, Canada, Puerto Rico, Australia, New Zealand
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous... and other conditionsUnited States
-
Wake Forest University Health SciencesWithdrawnLung Metastases | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Recurrent Malignant Mesothelioma | Advanced Malignant Mesothelioma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Recruiting
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | Neuropathy | COVID-19 InfectionUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingCervical Carcinoma | Endometrial Carcinoma | Vaginal Carcinoma | Malignant Female Reproductive System Neoplasm | Vulvar CarcinomaUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingMetastatic Colorectal Carcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 and other conditionsUnited States