Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01229111
First received: October 26, 2010
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

This phase II trial is studying how well giving cediranib maleate together with combination chemotherapy works in treating patients with advanced biliary cancers. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cediranib maleate together with combination chemotherapy may kill more tumor cells.


Condition Intervention Phase
Adult Primary Cholangiocellular Carcinoma
Advanced Adult Primary Liver Cancer
Cholangiocarcinoma of the Extrahepatic Bile Duct
Cholangiocarcinoma of the Gallbladder
Localized Unresectable Adult Primary Liver Cancer
Periampullary Adenocarcinoma
Recurrent Adult Primary Liver Cancer
Recurrent Extrahepatic Bile Duct Cancer
Recurrent Gallbladder Cancer
Unresectable Extrahepatic Bile Duct Cancer
Unresectable Gallbladder Cancer
Drug: cediranib maleate
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD2171 (Cediranib) With Modified FOLFOX6 in Patients With Advanced Biliary Cancers

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Estimation of the response rate of patients with advanced biliary cancers treated with cediranib maleate and modified FOLFOX6 evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated based on the number of responses using a binomial distribution and its confidence intervals will be estimated using Wilson's method. The 95% confidence intervals should be provided.


Secondary Outcome Measures:
  • Tabulation of the toxicity profile of the combination therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Estimation of the time to disease progression evaluated using the RECIST v1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Estimation of overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Identification of factors that predict survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Factors that predict survival will be identified by Cox model or extended Cox model.


Estimated Enrollment: 36
Study Start Date: October 2010
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: cediranib maleate
Given PO
Other Names:
  • AZD2171
  • Recentin
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01229111

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Ireland Cancer Center Landerbrook Health Center
Mayfield Heights, Ohio, United States, 44124
Lake University Ireland Cancer Center
Mentor, Ohio, United States, 44060
Southwest General Health Center Ireland Cancer Center
Middleburg Heights, Ohio, United States, 44130
UHHS-Chagrin Highlands Medical Center
Orange Village, Ohio, United States, 44122
Firelands Regional Medical Center
Sandusky, Ohio, United States, 44870
Ireland Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, United States, 44870
UH-Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio, United States, 44145
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Smitha Krishnamurthi Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01229111     History of Changes
Other Study ID Numbers: NCI-2011-02535, NCI-2011-02535, CDR0000687126, CWRU-CASE-9209, CASE 9209, 8323, N01CM00070, U01CA062502
Study First Received: October 26, 2010
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Liver Neoplasms
Gallbladder Neoplasms
Bile Duct Neoplasms
Cholangiocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Biliary Tract Neoplasms
Biliary Tract Diseases
Gallbladder Diseases
Bile Duct Diseases
Maleic acid
Cediranib
Levoleucovorin
Fluorouracil
Oxaliplatin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antidotes
Protective Agents
Physiological Effects of Drugs
Antimetabolites
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 30, 2014