- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01229111
Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers
A Phase 2 Study of AZD2171 (Cediranib) With Modified FOLFOX6 in Patients With Advanced Biliary Cancers
Study Overview
Status
Conditions
- Advanced Adult Primary Liver Cancer
- Localized Unresectable Adult Primary Liver Cancer
- Recurrent Adult Primary Liver Cancer
- Recurrent Extrahepatic Bile Duct Cancer
- Recurrent Gallbladder Cancer
- Unresectable Extrahepatic Bile Duct Cancer
- Unresectable Gallbladder Cancer
- Cholangiocarcinoma of the Extrahepatic Bile Duct
- Cholangiocarcinoma of the Gallbladder
- Adult Primary Cholangiocellular Carcinoma
- Periampullary Adenocarcinoma
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the response rate to AZD2171 (cediranib maleate) and modified folinic acid-fluorouracil-oxaliplatin-6 regimen (FOLFOX 6) in subjects with advanced biliary cancers.
SECONDARY OBJECTIVES:
I. To determine overall assessment of toxicity of AZD2171 and modified FOLFOX6. II. To determine the progression-free survival of subjects with advanced biliary cancers treated with AZD2171 and modified FOLFOX6.
III. To determine overall survival of subjects with advanced biliary cancers treated with AZD2171 and modified FOLFOX6.
OUTLINE:
Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-14 and modified FOLFOX6 comprising oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
-
Cleveland, Ohio, United States, 44106
- Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
-
Columbus, Ohio, United States, 43210
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
-
Mayfield Heights, Ohio, United States, 44124
- Ireland Cancer Center Landerbrook Health Center
-
Mentor, Ohio, United States, 44060
- Lake University Ireland Cancer Center
-
Orange Village, Ohio, United States, 44122
- UHHS-Chagrin Highlands Medical Center
-
Westlake, Ohio, United States, 44145
- UH-Seidman Cancer Center at Saint John Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with histopathological or cytopathological diagnosis of advanced biliary carcinoma (gallbladder cancer, cholangiocarcinoma, ampullary cancer) not amenable to conventional surgical approach are eligible
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
- No patients with untreated brain metastases
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Life expectancy of greater than 12 weeks
- White blood cell (WBC)/leukocytes ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 3 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 times institutional upper limit of normal
- Creatinine within normal institutional limits OR calculated creatinine clearance ≥ 60 mL/min
No patients with proteinuria not meeting the criteria below; urine sample must be tested by urine protein:creatinine (UPC) ratio or by urinalysis method within 1 week of starting study treatment; depending upon the testing method used, the following criteria must be met:
- UPC ratio must be < 1.0; if UPC ratio is ≥ 1.0, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein
- Urinalysis must indicate 0-1+ protein; if urinalysis reading is ≥ 2+, a 24-hour urine specimen must be collected and must demonstrate < 1 g of protein
- Not pregnant or nursing
- Negative pregnancy test
Fertile patients must use adequate contraception (hormonal or barrier method of birth control; abstinence) before and during study treatment
- Acceptable contraception includes abstinence, oral contraceptives, intra-uterine device (IUD), diaphragm, Norplant, approved hormone injections, condoms, or documentation of medical sterilization
Patients with evidence of heart disease must be New York Heart Association (NYHA) Class I or II
- NYHA Class II patients controlled with treatment are considered at increased risk for compromised left ventricular ejection fraction (LVEF) and will undergo increased cardiac monitoring
No patients with other active invasive cancers except nonmelanoma skin cancer or carcinoma in-situ of the cervix
- History of prior cancer is allowed as long as there has been no evidence of disease within the past 5 years
- No patients with mean corrected QT interval (QTc) > 480 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
No patients with uncontrolled hypertension defined as systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg, with or without anti-hypertensive medication or history of hypertensive crisis or hypertensive encephalopathy
- Patients with initial BP elevations are eligible once their BP is controlled to above parameters
No patients with uncontrolled intercurrent illness including, but not limited to:
- Hypertension (> 140/90 mm Hg)
- Chronic or active infection requiring chronic suppressive antibiotics
- History of or symptomatic congestive heart failure requiring chronic medical therapy
- NYHA class III or IV heart disease
- Unstable angina pectoris within 180 days prior to starting study treatment
- Myocardial infarction within 180 days prior to study treatment
- Gastroduodenal ulcer(s) determined by endoscopy to be active within 180 days prior to study treatment
- Serious or non-healing wound, skin ulcers, or bone fracture
- Any significant bleeding that is not related to the primary tumor within 180 days prior to study treatment
- Known bleeding diathesis or coagulopathy
- Paresthesias, peripheral sensory neuropathy > gr. 1 per Common Terminology Criteria for Adverse Events (CTCAE) v.4, or peripheral motor neuropathy ≥ gr. 2 per CTCAE v.4
- Psychiatric illness/social situations that would limit compliance with study requirements
- No patients with history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 180 days prior to study treatment, symptomatic peripheral ischemia; history of arterial thrombotic event within 180 days prior to study treatment; gastrointestinal (GI) perforation within 180 days prior to study treatment
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients who are chemotherapy naive unless chemotherapy was given as adjuvant post-surgical treatment and at least 6 months have elapsed since adjuvant chemotherapy
- No patients who have had major surgical procedures, open biopsies, or significant traumatic injury within 28 days prior to study treatment
- Chemotherapy for prior cancer is permitted
Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator
- Efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications
- Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 30 days
- Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
- Patients may not be receiving therapeutic doses of Coumadin or equivalent
- No patients requiring drugs with proarrhythmic potential
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 (cediranib maleate and modified FOLFOX)
Patients receive cediranib maleate PO QD on days 1-14 and modified FOLFOX6 comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Response Rate of Patients Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to 3 years
|
The number of patients with a Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
(Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tabulation of the Toxicity Profile of the Combination Therapy
Time Frame: Up to 3 years
|
Number of patients that experienced >/= grade 3 treatment related toxicities (definite, probable, possible).
|
Up to 3 years
|
Progression Free Survival
Time Frame: Up to 3 years
|
Time in months that evaluable subjects survived progression free
|
Up to 3 years
|
Estimation of Overall Survival
Time Frame: Up to 3 years
|
Time of overall response
|
Up to 3 years
|
Identification of Factors That Predict Survival
Time Frame: Up to three years
|
Factors that predict survival will be identified by Cox model or extended Cox model.
|
Up to three years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Smitha Krishnamurthi, Case Comprehensive Cancer Center
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 by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Digestive System Neoplasms
- Liver Diseases
- Gallbladder Diseases
- Biliary Tract Diseases
- Bile Duct Diseases
- Biliary Tract Neoplasms
- Recurrence
- Cholangiocarcinoma
- Liver Neoplasms
- Gallbladder Neoplasms
- Bile Duct Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Protein Kinase Inhibitors
- Vitamins
- Calcium-Regulating Hormones and Agents
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Oxaliplatin
- Leucovorin
- Calcium
- Levoleucovorin
- Cediranib
Other Study ID Numbers
- NCI-2011-02535 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- U01CA062502 (U.S. NIH Grant/Contract)
- N01CM00070 (U.S. NIH Grant/Contract)
- CDR0000687126
- CASE 9209 (OTHER: Case Comprehensive Cancer Center)
- 8323 (OTHER: CTEP)
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 Advanced Adult Primary Liver Cancer
-
University of HawaiiGlaxoSmithKlineRecruitingAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Adult Primary Liver CancerUnited States
-
University of CincinnatiActive, not recruitingLiver Metastases | Advanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver CancerUnited States
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)TerminatedAdvanced Adult Primary Liver Cancer | Localized Resectable Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Adult Primary Hepatocellular Carcinoma | Stage A Adult Primary Liver Cancer (BCLC) | Stage B Adult Primary Liver Cancer (BCLC)United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Resectable Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States, Singapore
-
University of WashingtonNational Cancer Institute (NCI)TerminatedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver Cancer | Adult Primary Hepatocellular CarcinomaUnited States
Clinical Trials on oxaliplatin
-
Xijing HospitalUnknownGastrointestinal CancerChina
-
Lin ChenUnknownGastric AdenocarcinomaChina
-
Samsung Medical CenterNational Cancer Center, Korea; Asan Medical Center; Chonnam National University... and other collaboratorsCompletedColorectal CancerKorea, Republic of
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Cancer | Primary Peritoneal Cavity CancerUnited States, Canada
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical CancerUnited States, Canada
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedHead and Neck CancerUnited States
-
St. Jude Children's Research HospitalNational Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol SpecificUnited States
-
Gustave Roussy, Cancer Campus, Grand ParisNational Cancer Institute, FranceSuspended
-
University of ChicagoNational Cancer Institute (NCI)CompletedBladder Cancer | Transitional Cell Cancer of the Renal Pelvis and UreterUnited States, Canada
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedEndometrial CancerUnited States