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

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ClinicalTrials.gov Identifier: NCT01229111
Recruitment Status : Terminated (Lack of Drug Supply)
First Posted : October 27, 2010
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions Drug: cediranib maleate
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Enrollment 14

Recruitment Details Patients were recruited from hospitals in Cleveland and Columbus, Ohio from October 2010 through February 2013.
Pre-assignment Details  
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
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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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Period Title: Overall Study
Started 14
Completed 13
Not Completed 1
Reason Not Completed
Death             1
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Baseline Participants 14
Hide Baseline Analysis Population Description
All patients who signed consent.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants
30-39 years 1
40-49 years 1
50-59 years 3
60-69 years 8
70-79 years 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Female
11
  78.6%
Male
3
  21.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
14
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   7.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  14.3%
White
11
  78.6%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants
14
1.Primary Outcome
Title The Response Rate of Patients Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Hide Description 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.
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients that were evaluable
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description:

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
Partial Response (PR) 4
Stable Disease (SD) 6
Progressive Disease (PD) 1
2.Secondary Outcome
Title Tabulation of the Toxicity Profile of the Combination Therapy
Hide Description Number of patients that experienced >/= grade 3 treatment related toxicities (definite, probable, possible).
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients that received treatment drug
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description:

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: participants
11
3.Secondary Outcome
Title Progression Free Survival
Hide Description Time in months that evaluable subjects survived progression free
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients that were evaluable for response
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description:

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Months
14.4
(3 to 22.5)
4.Secondary Outcome
Title Estimation of Overall Survival
Hide Description Time of overall response
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients that received treatment.
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description:

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Months
19.2
(3 to 31.3)
5.Secondary Outcome
Title Identification of Factors That Predict Survival
Hide Description Factors that predict survival will be identified by Cox model or extended Cox model.
Time Frame Up to three years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Statistically, due to the small sample size, analysis could not be done
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description:

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Patients were followed for adverse events from start of treatment until resolved for about 3 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Cediranib Maleate and Modified FOLFOX)
Hide Arm/Group Description

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.

cediranib maleate: Given PO

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

All-Cause Mortality
Treatment (Cediranib Maleate and Modified FOLFOX)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Cediranib Maleate and Modified FOLFOX)
Affected / at Risk (%)
Total   11/13 (84.62%) 
Blood and lymphatic system disorders   
Anemia * 1  1/13 (7.69%) 
Fibrile Neutropenia * 1  1/13 (7.69%) 
Gastrointestinal disorders   
Abdominal Pain * 1  1/13 (7.69%) 
Ascites * 1  1/13 (7.69%) 
Colitis * 1  1/13 (7.69%) 
Diarrhea * 1  1/13 (7.69%) 
Duodenal hemorrage * 1  1/13 (7.69%) 
Duodenal ulcer * 1  1/13 (7.69%) 
Duodenal Obstruction * 1  1/13 (7.69%) 
Nausea * 1  2/13 (15.38%) 
Vomiting * 1  2/13 (15.38%) 
Abscess * 1  1/13 (7.69%) 
General disorders   
Death * 1  2/13 (15.38%) 
Fatigue * 1  1/13 (7.69%) 
Infections and infestations   
Biliary Tract infection * 1  1/13 (7.69%) 
Skin Infection * 1  1/13 (7.69%) 
Lung Infection * 1  1/13 (7.69%) 
Injury, poisoning and procedural complications   
Catheter related infection * 1  2/13 (15.38%) 
Fall * 1  1/13 (7.69%) 
Vascular access complication * 1  1/13 (7.69%) 
Investigations   
Neutrophil count decreased * 1  3/13 (23.08%) 
Platelet count decreased * 1  2/13 (15.38%) 
Metabolism and nutrition disorders   
Hypocalcemia * 1  1/13 (7.69%) 
Hypokalemia * 1  3/13 (23.08%) 
Musculoskeletal and connective tissue disorders   
Generalized muscle weakness * 1  2/13 (15.38%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified * 1 [1]  1/13 (7.69%) 
Nervous system disorders   
Altered mental status * 1  1/13 (7.69%) 
Pregnancy, puerperium and perinatal conditions   
Confusion * 1  1/13 (7.69%) 
Renal and urinary disorders   
Urinary tract infection * 1  1/13 (7.69%) 
Acute kidney injury * 1  1/13 (7.69%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v4.0
[1]
Disease Progression
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Cediranib Maleate and Modified FOLFOX)
Affected / at Risk (%)
Total   13/13 (100.00%) 
Blood and lymphatic system disorders   
Anemia * 1  9/13 (69.23%) 
Leukocytosis * 1  1/13 (7.69%) 
Cardiac disorders   
Aortic valve disease * 1  1/13 (7.69%) 
Atrial fibrillation * 1  1/13 (7.69%) 
Catheter related infection * 1  2/13 (15.38%) 
Ear and labyrinth disorders   
Ear and labyrinth disorders - Other, specify * 1  1/13 (7.69%) 
Tinnitus * 1  2/13 (15.38%) 
Eye disorders   
Blurred vision * 1  1/13 (7.69%) 
Gastrointestinal disorders   
Abdominal distension * 1  2/13 (15.38%) 
Abdominal pain * 1  11/13 (84.62%) 
Anal hemorrhage * 1  1/13 (7.69%) 
Confusion * 1  1/13 (7.69%) 
Depression * 1  4/13 (30.77%) 
Dizziness * 1  8/13 (61.54%) 
Duodenal ulcer * 1  1/13 (7.69%) 
Dysphagia * 1  1/13 (7.69%) 
Gastrointestinal disorders - Other, specify * 1  2/13 (15.38%) 
Hemorrhoids * 1  1/13 (7.69%) 
Mucositis oral * 1  8/13 (61.54%) 
Nausea * 1  11/13 (84.62%) 
Oral dysesthesia * 1  1/13 (7.69%) 
Oral pain * 1  2/13 (15.38%) 
Rectal hemorrhage * 1  2/13 (15.38%) 
Vomiting * 1  6/13 (46.15%) 
General disorders   
Edema limbs * 1  5/13 (38.46%) 
Facial pain * 1  1/13 (7.69%) 
Fatigue * 1  11/13 (84.62%) 
Fever * 1  2/13 (15.38%) 
Non-cardiac chest pain * 1  2/13 (15.38%) 
Immune system disorders   
Allergic reaction * 1  1/13 (7.69%) 
Infections and infestations   
Biliary tract infection * 1  1/13 (7.69%) 
Infections and infestations - thrush * 1  3/13 (23.08%) 
Skin infection * 1  2/13 (15.38%) 
Urinary tract infection * 1  3/13 (23.08%) 
Injury, poisoning and procedural complications   
Bruising * 1  1/13 (7.69%) 
Wound dehiscence * 1  1/13 (7.69%) 
Investigations   
Alanine aminotransferase increased * 1  9/13 (69.23%) 
Alkaline phosphatase increased * 1  13/13 (100.00%) 
Aspartate aminotransferase increased * 1  10/13 (76.92%) 
Blood bilirubin increased * 1  5/13 (38.46%) 
Cough * 1  2/13 (15.38%) 
Hemoglobin increased * 1  1/13 (7.69%) 
Lymphocyte count decreased * 1  6/13 (46.15%) 
elevated LDH * 1  4/13 (30.77%) 
Neutrophil count decreased * 1  9/13 (69.23%) 
Platelet count decreased * 1  12/13 (92.31%) 
Weight loss * 1  7/13 (53.85%) 
White blood cell decreased * 1  10/13 (76.92%) 
Metabolism and nutrition disorders   
Anorexia * 1  11/13 (84.62%) 
Creatinine increased * 1  2/13 (15.38%) 
Hypercalcemia * 1  2/13 (15.38%) 
Hyperglycemia * 1  6/13 (46.15%) 
Hyperkalemia * 1  1/13 (7.69%) 
Hypermagnesemia * 1  1/13 (7.69%) 
Hypernatremia * 1  1/13 (7.69%) 
Hypoalbuminemia * 1  7/13 (53.85%) 
Hypocalcemia * 1  8/13 (61.54%) 
Hypokalemia * 1  8/13 (61.54%) 
Hypomagnesemia * 1  4/13 (30.77%) 
Hyponatremia * 1  11/13 (84.62%) 
Hypophosphatemia * 1  7/13 (53.85%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  2/13 (15.38%) 
Back pain * 1  5/13 (38.46%) 
Bone pain * 1  1/13 (7.69%) 
Flank pain * 1  1/13 (7.69%) 
Generalized muscle weakness * 1  6/13 (46.15%) 
Muscle weakness * 1  3/13 (23.08%) 
Neck pain * 1  1/13 (7.69%) 
Pain in extremity * 1  2/13 (15.38%) 
Nervous system disorders   
Diarrhea * 1  8/13 (61.54%) 
Dysarthria * 1  1/13 (7.69%) 
Dysgeusia * 1  4/13 (30.77%) 
Headache * 1  2/13 (15.38%) 
Nervous system disorders - cold sensitivity * 1  2/13 (15.38%) 
Paresthesia * 1  1/13 (7.69%) 
Peripheral sensory neuropathy * 1  11/13 (84.62%) 
Psychiatric disorders   
Anxiety * 1  6/13 (46.15%) 
Chest pain - cardiac * 1  1/13 (7.69%) 
Dehydration * 1  3/13 (23.08%) 
Insomnia * 1  10/13 (76.92%) 
Renal and urinary disorders   
Hematuria * 1  3/13 (23.08%) 
Proteinuria * 1  6/13 (46.15%) 
Urinary tract pain * 1  1/13 (7.69%) 
Reproductive system and breast disorders   
Vaginal hemorrhage * 1  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis * 1  1/13 (7.69%) 
Constipation * 1  8/13 (61.54%) 
Dyspnea * 1  7/13 (53.85%) 
Epistaxis * 1  3/13 (23.08%) 
Hoarseness * 1  4/13 (30.77%) 
Nasal congestion * 1  1/13 (7.69%) 
Postnasal drip * 1  1/13 (7.69%) 
Sore throat * 1  1/13 (7.69%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  6/13 (46.15%) 
Dry mouth * 1  2/13 (15.38%) 
Erythroderma * 1  1/13 (7.69%) 
Nail discoloration * 1  1/13 (7.69%) 
Pain of skin * 1  1/13 (7.69%) 
Palmar-plantar erythrodysesthesia syndrome * 1  7/13 (53.85%) 
Pruritus * 1  1/13 (7.69%) 
Rash acneiform * 1  2/13 (15.38%) 
Rash maculo-papular * 1  1/13 (7.69%) 
Skin hyperpigmentation * 1  4/13 (30.77%) 
Vascular disorders   
Flushing * 1  1/13 (7.69%) 
Hot flashes * 1  6/13 (46.15%) 
Hypertension * 1  6/13 (46.15%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE v4.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Smitha Krishnamurthi
Organization: Case Comprehensive Cancer Center
Phone: 216-844-5234
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01229111     History of Changes
Other Study ID Numbers: NCI-2011-02535
NCI-2011-02535 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000687126
CASE 9209 ( Other Identifier: Case Comprehensive Cancer Center )
8323 ( Other Identifier: CTEP )
N01CM00070 ( U.S. NIH Grant/Contract )
U01CA062502 ( U.S. NIH Grant/Contract )
First Submitted: October 26, 2010
First Posted: October 27, 2010
Results First Submitted: February 10, 2017
Results First Posted: March 29, 2017
Last Update Posted: March 29, 2017