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Trial record 49 of 104 for:    colon cancer | ( Map: Nebraska, United States )

A Trial of Single Agent Axitinib as Maintenance Therapy for Patients With First Line Metastatic Colorectal Cancer (mCRC)

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ClinicalTrials.gov Identifier: NCT01490866
Recruitment Status : Completed
First Posted : December 13, 2011
Results First Posted : January 12, 2017
Last Update Posted : January 12, 2017
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: Axitinib
Drug: Bevacizumab
Drug: 5-Fluorouracil
Drug: Leucovorin
Drug: Oxaliplatin
Enrollment 70
Recruitment Details Between January 2012 and January 2014, 70 patients with histologically or cytologically confirmed metastatic carcinoma of colon or rectum were enrolled and treated. The trial was conducted at 12 sites in the United States.
Pre-assignment Details In this non-randomized open label trial, patients began treatment with FOLFOX/bevacizumab every 4 weeks for 16 weeks. Patients with objective response or stable disease began Axitinib maintenance therapy at week 17. Axitinib therapy continued until disease progression, unacceptable toxicity or did not meet any criteria for discontinuation.
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
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All patients receive FOLFOX/bevacizumab for four 28-day cycles (16 weeks). After 4 cycles, axitinib maintenance will be administered starting on Week 17. Maintenance treatment will continue until disease progression or intolerable toxicity occurs.

FOLFOX/bevacizumab ( FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin):

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day on Days 1 thru 28 of each cycle until disease progression or unacceptable toxicity occurs.

Period Title: FOLFOX/Bevacizumab Treatment
Started 70
Completed 49
Not Completed 21
Reason Not Completed
Disease Progression             6
Adverse Event             6
Withdrawal by Subject             5
Protocol Violation             1
Intercurrent illness             1
Physician Decision             2
Period Title: Axitinib Maintenance Therapy
Started 49
Completed 0 [1]
Not Completed 49
Reason Not Completed
Disease Progression             30
Adverse Event             12
Withdrawal by Subject             3
Protocol Violation             2
Intercurrent illness             2
[1]
No protocol defined endpoint to Axitinib maintenance treatment.
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
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All patients receive FOLFOX/bevacizumab for four 28-day cycles (a total of 16 weeks). After 4 cycles, axitinib maintenance will be administered. FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin.

FOLFOX/bevacizumab:

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by;IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day (PO BID)

Overall Number of Baseline Participants 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 70 participants
60
(36 to 90)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants
Female
34
  48.6%
Male
36
  51.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 70 participants
Caucasian 62
Black/African American 6
Asian 1
Unknown 1
1.Primary Outcome
Title Progression-free Survival
Time Frame 24 months
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All patients who received at least one dose of any study drug.
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
Hide Arm/Group Description:

All patients receive FOLFOX/bevacizumab for four 28-day cycles (16 weeks). After 4 cycles, axitinib maintenance will be administered starting on Week 17. Maintenance treatment will continue until disease progression or intolerable toxicity occurs.

FOLFOX/bevacizumab ( FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin):

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day on Days 1 thru 28 of each cycle until disease progression or unacceptable toxicity occurs.

Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: months
8.3
(7.8 to 9.4)
2.Secondary Outcome
Title Objective Response Rate
Hide Description Defined as the percentage of evaluable patients showing a complete or partial response (CR or PR) per RECIST v1.1 criteria. CR = disappearance of all lesions. PR = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since start of treatment.
Time Frame every 8 weeks, assessed up to approximately 24 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
Hide Arm/Group Description:

All patients receive FOLFOX/bevacizumab for four 28-day cycles (a total of 16 weeks). After 4 cycles, axitinib maintenance will be administered. FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin.

FOLFOX/bevacizumab:

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by;IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day (PO BID)

Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
Objective Response 34
Stable Disease 57
3.Secondary Outcome
Title Time To Progression (TTP)
Hide Description Defined as the time after a disease is diagnosed (or treated) until worsening of the disease.
Time Frame every 8 weeks, assessed approximately up to 24 months
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
Hide Arm/Group Description:

All patients receive FOLFOX/bevacizumab for four 28-day cycles (16 weeks). After 4 cycles, axitinib maintenance will be administered starting on Week 17. Maintenance treatment will continue until disease progression or intolerable toxicity occurs.

FOLFOX/bevacizumab ( FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin):

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day on Days 1 thru 28 of each cycle until disease progression or unacceptable toxicity occurs.

Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: months
8.8
(8.1 to 10.2)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as the time from first treatment until death from any cause.
Time Frame every 8 weeks until progression then every 3 months for up to 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
Hide Arm/Group Description:

All patients receive FOLFOX/bevacizumab for four 28-day cycles (16 weeks). After 4 cycles, axitinib maintenance will be administered starting on Week 17. Maintenance treatment will continue until disease progression or intolerable toxicity occurs.

FOLFOX/bevacizumab ( FOLFOX is a combination of Leucovorin, fluorouracil and oxiloplatin):

  • 5-Fluorouracil: 400 mg/m2 Days 1 and 15 by IV followed by 2400 mg/m2 over 46-48 hours Days 1 and 15 by continuous infusion;
  • Leucovorin: 400 mg/m2 given Days 1 and 15 by IV
  • Oxaliplatin: 85 mg/m2 Days 1 and 15 by IV
  • Bevacizumab: 5 mg/kg on Days 1 and 15 by IV

Maintenance:

- Axitinib: 5-mg tablets orally twice per day on Days 1 thru 28 of each cycle until disease progression or unacceptable toxicity occurs.

Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: months
24.2
(16.0 to 30.9)
5.Secondary Outcome
Title Frequency of Adverse Events as a Measure of Safety
Hide Description The frequency of adverse events (AEs) was analyzed in 2 groups of patients, those receiving FOLFOX/bevacizumab (N=70), and patients who received axitinib maintenance (N = 48). AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Time Frame Every 4 weeks plus 30 days during treatment and up to 5 years thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title FOLFOX/Bevacizumab Axitinib
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All patients who received at least one dose of FOLFOX/bevacizumab
All patients who received at least one dose of axitinib
Overall Number of Participants Analyzed 70 49
Measure Type: Number
Unit of Measure: participants
Fatigue 40 24
Nausea 37 15
Diarrhea 34 16
Peripheral neuropathy 34 16
Neutropenia 25 0
Thrombocytopenia 22 8
Leukopenia 21 7
Anorexia 19 14
Mucositis 18 5
Proteinuria 16 12
Anemia 16 7
Constipation 15 0
Pain 14 11
Vomiting 14 0
Hypertension 11 22
Headache 9 7
Myalgia 8 10
Dizziness 8 0
Skin changes 7 0
Arthralgia 7 6
Hand-foot skin reaction 0 7
Dyspnea 0 7
Hoarseness 0 7
AST increased 0 5
Time Frame Up to 3 years
Adverse Event Reporting Description Safety population included all patients who received at least one dose of any study drug.
 
Arm/Group Title FOLFOX/Bevacizumab and Axitinib
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
FOLFOX/Bevacizumab and Axitinib
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
FOLFOX/Bevacizumab and Axitinib
Affected / at Risk (%) # Events
Total   13/70 (18.57%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/70 (1.43%)  1
Thrombocytopenia  1  1/70 (1.43%)  1
Cardiac disorders   
Tachycardia  1  1/70 (1.43%)  2
Cardio-respiratory arrest  1  1/70 (1.43%)  1
Sinus bradycardia  1  1/70 (1.43%)  1
Ventricular fibrillation  1  1/70 (1.43%)  1
Ventricular tachycardia  1  1/70 (1.43%)  1
Gastrointestinal disorders   
Diarrhoea  1  1/70 (1.43%)  2
Intestinal obstruction  1  1/70 (1.43%)  2
Enteritis  1  1/70 (1.43%)  1
Large intestinal obstruction  1  1/70 (1.43%)  1
Nausea  1  1/70 (1.43%)  1
Rectal haemorrhage  1  1/70 (1.43%)  1
Small intestinal obstruction  1  1/70 (1.43%)  1
Vomiting  1  1/70 (1.43%)  1
General disorders   
Chest pain  1 [1]  2/70 (2.86%)  2
Asthenia  1  1/70 (1.43%)  1
Fatigue  1  1/70 (1.43%)  1
Pain  1  1/70 (1.43%)  1
Infections and infestations   
Clostridium difficile colitis  1  2/70 (2.86%)  2
Urinary tract infection  1  2/70 (2.86%)  2
Bronchitis  1  1/70 (1.43%)  1
Systemic candida  1  1/70 (1.43%)  1
Injury, poisoning and procedural complications   
Fall  1  1/70 (1.43%)  1
Fracture  1  1/70 (1.43%)  1
Investigations   
International normalised ratio increased  1  1/70 (1.43%)  1
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/70 (1.43%)  1
Back pain  1  1/70 (1.43%)  1
Musculoskeletal pain  1  1/70 (1.43%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour flare  1  1/70 (1.43%)  1
Nervous system disorders   
Cerebrovascular accident  1  1/70 (1.43%)  1
Encephalopathy  1  1/70 (1.43%)  1
Posterior reversible encephalopathy syndrome  1  1/70 (1.43%)  1
Syncope  1  1/70 (1.43%)  1
Renal and urinary disorders   
Ureteric obstruction  1  1/70 (1.43%)  1
Respiratory, thoracic and mediastinal disorders   
Respiratory failure  1  1/70 (1.43%)  1
Vascular disorders   
Accelerated hypertension  1  1/70 (1.43%)  1
Deep vein thrombosis  1  1/70 (1.43%)  1
Embolism  1  1/70 (1.43%)  1
Hypertension  1  1/70 (1.43%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
There were two treatment-related deaths on study, due to reversible posterior leukoencephalopathy syndrome (RPLS) and febrile neutropenia/thrombocytopenia
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FOLFOX/Bevacizumab and Axitinib
Affected / at Risk (%) # Events
Total   70/70 (100.00%)    
Blood and lymphatic system disorders   
Anemia * 1  18/70 (25.71%) 
Leukopenia * 1  25/70 (35.71%) 
Neutropenia * 1  26/70 (37.14%) 
Thrombocytopenia * 1  25/70 (35.71%) 
Endocrine disorders   
Hypothyroidism * 1  4/70 (5.71%) 
Gastrointestinal disorders   
Abdominal Pain * 1  9/70 (12.86%) 
Constipation * 1  18/70 (25.71%) 
Diarrhea * 1  40/70 (57.14%) 
Dyspepsia * 1  7/70 (10.00%) 
Gastroesophageal Reflux Disease * 1  5/70 (7.14%) 
Mucositis * 1  18/70 (25.71%) 
Nausea * 1  39/70 (55.71%) 
Oral Pain * 1  7/70 (10.00%) 
Sore Throat * 1  5/70 (7.14%) 
Vomiting * 1  17/70 (24.29%) 
General disorders   
Asthenia * 1  7/70 (10.00%) 
Chills * 1  4/70 (5.71%) 
Cold Intolerance * 1  4/70 (5.71%) 
Edema * 1  5/70 (7.14%) 
Fatigue * 1  48/70 (68.57%) 
Hemorrhage * 1  4/70 (5.71%) 
Temperature Intolerance * 1  4/70 (5.71%) 
Immune system disorders   
Allergic Reaction * 1  6/70 (8.57%) 
Investigations   
Alanine Aminotransferase Increased * 1  5/70 (7.14%) 
Alkaline Phosphatase Increased * 1  5/70 (7.14%) 
Aspartate Aminotransferase Increased * 1  5/70 (7.14%) 
Weight Loss * 1  7/70 (10.00%) 
Metabolism and nutrition disorders   
Anorexia * 1  24/70 (34.29%) 
Dehydration * 1  7/70 (10.00%) 
Hypokalemia * 1  7/70 (10.00%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  10/70 (14.29%) 
Myalgia * 1  13/70 (18.57%) 
Pain In Extremity * 1  7/70 (10.00%) 
Nervous system disorders   
Dizziness * 1  9/70 (12.86%) 
Dysesthesia * 1  4/70 (5.71%) 
Dysgeusia * 1  5/70 (7.14%) 
Headache * 1  14/70 (20.00%) 
Insomnia * 1  4/70 (5.71%) 
Paresthesia * 1  5/70 (7.14%) 
Peripheral Neuropathy * 1  41/70 (58.57%) 
Taste Alteration * 1  4/70 (5.71%) 
Renal and urinary disorders   
Proteinuria * 1  20/70 (28.57%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  4/70 (5.71%) 
Dyspnea * 1  8/70 (11.43%) 
Epistaxis * 1  6/70 (8.57%) 
Hoarseness * 1  8/70 (11.43%) 
Sinusitis * 1  4/70 (5.71%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  6/70 (8.57%) 
Palmar-Plantar Erythrodysesthesia Syndrome * 1  10/70 (14.29%) 
Rash * 1  8/70 (11.43%) 
Skin Changes * 1  10/70 (14.29%) 
Vascular disorders   
Hypertension * 1  27/70 (38.57%) 
*
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.
The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Results Point of Contact
Name/Title: Charles H. Davis, RAC
Organization: SCRI Development Innovations
Phone: 615 524-4341
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01490866     History of Changes
Other Study ID Numbers: SCRI GI 154
First Submitted: November 7, 2011
First Posted: December 13, 2011
Results First Submitted: September 21, 2016
Results First Posted: January 12, 2017
Last Update Posted: January 12, 2017