Ignite Creation Date:
2024-05-05 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00464295
Status:
COMPLETED
Last Update Posted:
2007-12-14
First Post:
2007-04-20
Brief Title:
Phase II Trial of Capecitabine for the Treatment of Unresectable Metastatic or Advanced Hepatocellular CarcinomaHCC
Sponsor:
Aga Khan University
Organization:
Aga Khan University
Study Overview
Official Title:
Phase II Trial of Capecitabine for the Treatment of Unresectable Metastatic or Advanced Hepatocellular CarcinomaHCC
Status:
COMPLETED
Status Verified Date:
2007-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HCC-CAP
Brief Summary:
In patients with unresectableadvanced Hepatocellular Carcinoma receiving Capecitabin we anticipate that the proposed chemotherapy will have a delay in progression of the disease It is also expected that proposed chemotherapy will have acceptable toxicity and Quality of life
Detailed Description:
II OBJECTIVES
IIA Primary Objectives To evaluate response rate RR and overall survival OS
IIB Secondary Objective To evaluate the time to progression TTP median time to response MTR toxicity and quality of life QOL
III STUDY DESIGN
IIIA Inclusion criteria
1 Written informed consent 2 Age between 18 and 70 years 3 Documented by at least 2 out of three mentioned criteria and evidence of non-resectability
1 Radiological either CT ScanUS abdomen
2 Biopsy
3 Serum alphafeto protein level 4 Multi centric hepatoma or TNM Classification Stage IV 5 Childs class B or C with a Childs score of maximum 11 6 No other active malignancy except localized basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
7 Life expectancy of greater then 3 months 8 Current laboratory values must be within the limits listed below Haemoglobin 8 gdL WBC 4000uL Absolute Neutrophil Count 1500uL Platelets 75000uL 9 ECOG Performance status of 2 10 Patients who have received adjuvant or neoadjuvant therapy are eligible A minimum interval of 4 weeks since last chemotherapy will be required
11 Prior radiotherapy will be allowed if it did not involve a site used to assess response and 4 weeks have elapsed since completion of radiotherapy
IIIB Exclusion criteria
1 History of allergic reaction to compound chemically related to CAP 2 Concomitant or previous malignancies within five years other than basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix 3 Active uncontrolled infection 5 Concurrent medical problems which could limit the life expectancy or the ability of the patient to receive chemotherapy
6 Mental condition that could limit the patient in comprehending the concept of clinical trial or complying with its requirements
7 Brain or leptomeningeal involvement 8 Pre-existing neurotoxicity of grade 2 9 Concomitant radiotherapy unless localised for bone pain control or palliation
10 Being of reproductive potential and not agreeing to practice an effective contraceptive method
11 Pregnancy or lactation 12 Severe renal impairment with Creatinine clearance 30mlminute 13 Documented Cardiomyopathy or severe coronary artery disease or history of arrhythmias
IV PATIENT REGISTRATION
All patients entering this study must be registered by contacting
Drs Kashif AnisZaigham Abbas -Research Co-ordinators The Aga Khan University Hospital Dept of Medicine Medical Oncology Stadium Road PO Box 3500 Karachi 74800 Pakistan Tel 021 493-0051
V THERAPY
This is a Phase II trial studying chemotherapy with CAP in non-resectable HCC Prior chemotherapy radiation therapy surgery is permitted Staging is required with a CAT scanUltrasound of abdomen and bone scan if necessary Pre study evaluation should include CBC renal functions assessment and liver function tests Patients will require independent evaluation with medical oncologistgastroenterologist prior to being included in the study Chemotherapy would be given in cycles of 21 days CAP would be given as oral tablets twice daily starting from day 1 to day 14 Medication with standard anti-emetics which may include serotonin antagonist may be used before administration of chemotherapy Duration of chemotherapy administration would be determined by the patients response A patient who has progressive disease is not able to tolerate chemotherapy and has unacceptable toxicity would be taken off the study Patients who have a response will continue on chemotherapy till progression of disease or inability to tolerate chemotherapy is documented
VI DOSE MODIFICATION
Hematologic Toxicity
Chemotherapy will be held if ANC 1500uL andor platelet count is 50000uL Treatment will resume when counts recover Growth factors can be used in subsequent cycles if delay is secondary to neutropenia If there is no recovery after 3 weeks of delay the patient will be taken off the study
Renal dysfunction
Creatinine Clearance mLmin Dose 50 100 30-50 75 30 0no treatment is given
Elevated Liver Function Tests
In the event that bilirubin is elevated during the study the next cycle will be delayed by a maximum of 2 weeks The following dose modification in the dose of capecitabine will be made if the AST andor ALT andor alkaline phosphatase levels are elevated
ASTALT Alkaline Phosphatase Recommended dose 15- 25 x normal 25 x normal 75 25- 5 x normal 25- 5 x normal 50 5 x normal 5 x normal Dose delay by a maximum of 2 weeks If no recovery is noted the patient should go off study
Cardio toxicity
Significant drop in left ventricular ejection fraction andor clinical signs and symptoms of cardiac failure will result in discontinuation from the study
Dose Modification
Dose reduction is planned if significant Grade IIIIV hematologic or non-hematologic toxicities are observed CAP shall be reduced by 25 with grade IIIIV toxicity occur Patient should be taken off study if a life threatening complication occurs All grade IIIIV toxicities should be recorded in detail including the dates of onset and resolutionoutcome GI toxicity of grade II including severe diarrhea nausea vomiting and stomatitis dose modification will be done as it will be held for 1 week along with symptomatic treatment if no improvement for 2 weeks then patient will be taken off the study
VII SERIOUS ADVERSE EVENT REPORTING
All serious events as defined in Appendix E of protocol must be reported as soon as you are aware of them to
Drs Kashif AnisZaigham Abbas at the Aga Khan University Hospital VIII EVALUATION
Evaluation before Treatment
Patient should have evaluation by gastroenterologyoncology to determine eligibility
All Patients should have
Diagnosis of hepatoma with the help of Biopsy if possible or by the help of CT Scan or Serum alpha fetoprotein level fulfilling 2 out of 3 criteria
Complete history and physical examination CBC differential platelet count serum sodium potassium glucose calcium creatinine bilirubin alkaline phosphatase AST ALT alpha fetoproteinAFP prothrombin time PT and Serum Albumin
CT scan of the abdomen with contrast Cardiac evaluation of LVEF CT scans and plain x-rays if clinically indicated
Evaluation during Chemotherapy
CBC differential platelets count sodium potassium creatinine glucose bilirubin alkaline phosphatase ASTALT
CBC should be repeated prior to every chemotherapy course
Re-evaluation of response after every 3 courses of chemotherapy would be done radio logically by repeating a CT scanx rays as indicated by sites of disease involvement
Evaluation After chemotherapy
All patients will be followed thereafter cessation of chemotherapy due to progression of disease every three to six months until a total of five years for evaluation of five-year disease free and overall survival
Evaluation of toxicity profile
This should be based either on the NCIC common toxicity criteria attached at the end or any other major toxicity criteria eg NCI and documented in the attached form
IIA Primary Objectives To evaluate response rate RR and overall survival OS
IIB Secondary Objective To evaluate the time to progression TTP median time to response MTR toxicity and quality of life QOL
III STUDY DESIGN
IIIA Inclusion criteria
1 Written informed consent 2 Age between 18 and 70 years 3 Documented by at least 2 out of three mentioned criteria and evidence of non-resectability
1 Radiological either CT ScanUS abdomen
2 Biopsy
3 Serum alphafeto protein level 4 Multi centric hepatoma or TNM Classification Stage IV 5 Childs class B or C with a Childs score of maximum 11 6 No other active malignancy except localized basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
7 Life expectancy of greater then 3 months 8 Current laboratory values must be within the limits listed below Haemoglobin 8 gdL WBC 4000uL Absolute Neutrophil Count 1500uL Platelets 75000uL 9 ECOG Performance status of 2 10 Patients who have received adjuvant or neoadjuvant therapy are eligible A minimum interval of 4 weeks since last chemotherapy will be required
11 Prior radiotherapy will be allowed if it did not involve a site used to assess response and 4 weeks have elapsed since completion of radiotherapy
IIIB Exclusion criteria
1 History of allergic reaction to compound chemically related to CAP 2 Concomitant or previous malignancies within five years other than basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix 3 Active uncontrolled infection 5 Concurrent medical problems which could limit the life expectancy or the ability of the patient to receive chemotherapy
6 Mental condition that could limit the patient in comprehending the concept of clinical trial or complying with its requirements
7 Brain or leptomeningeal involvement 8 Pre-existing neurotoxicity of grade 2 9 Concomitant radiotherapy unless localised for bone pain control or palliation
10 Being of reproductive potential and not agreeing to practice an effective contraceptive method
11 Pregnancy or lactation 12 Severe renal impairment with Creatinine clearance 30mlminute 13 Documented Cardiomyopathy or severe coronary artery disease or history of arrhythmias
IV PATIENT REGISTRATION
All patients entering this study must be registered by contacting
Drs Kashif AnisZaigham Abbas -Research Co-ordinators The Aga Khan University Hospital Dept of Medicine Medical Oncology Stadium Road PO Box 3500 Karachi 74800 Pakistan Tel 021 493-0051
V THERAPY
This is a Phase II trial studying chemotherapy with CAP in non-resectable HCC Prior chemotherapy radiation therapy surgery is permitted Staging is required with a CAT scanUltrasound of abdomen and bone scan if necessary Pre study evaluation should include CBC renal functions assessment and liver function tests Patients will require independent evaluation with medical oncologistgastroenterologist prior to being included in the study Chemotherapy would be given in cycles of 21 days CAP would be given as oral tablets twice daily starting from day 1 to day 14 Medication with standard anti-emetics which may include serotonin antagonist may be used before administration of chemotherapy Duration of chemotherapy administration would be determined by the patients response A patient who has progressive disease is not able to tolerate chemotherapy and has unacceptable toxicity would be taken off the study Patients who have a response will continue on chemotherapy till progression of disease or inability to tolerate chemotherapy is documented
VI DOSE MODIFICATION
Hematologic Toxicity
Chemotherapy will be held if ANC 1500uL andor platelet count is 50000uL Treatment will resume when counts recover Growth factors can be used in subsequent cycles if delay is secondary to neutropenia If there is no recovery after 3 weeks of delay the patient will be taken off the study
Renal dysfunction
Creatinine Clearance mLmin Dose 50 100 30-50 75 30 0no treatment is given
Elevated Liver Function Tests
In the event that bilirubin is elevated during the study the next cycle will be delayed by a maximum of 2 weeks The following dose modification in the dose of capecitabine will be made if the AST andor ALT andor alkaline phosphatase levels are elevated
ASTALT Alkaline Phosphatase Recommended dose 15- 25 x normal 25 x normal 75 25- 5 x normal 25- 5 x normal 50 5 x normal 5 x normal Dose delay by a maximum of 2 weeks If no recovery is noted the patient should go off study
Cardio toxicity
Significant drop in left ventricular ejection fraction andor clinical signs and symptoms of cardiac failure will result in discontinuation from the study
Dose Modification
Dose reduction is planned if significant Grade IIIIV hematologic or non-hematologic toxicities are observed CAP shall be reduced by 25 with grade IIIIV toxicity occur Patient should be taken off study if a life threatening complication occurs All grade IIIIV toxicities should be recorded in detail including the dates of onset and resolutionoutcome GI toxicity of grade II including severe diarrhea nausea vomiting and stomatitis dose modification will be done as it will be held for 1 week along with symptomatic treatment if no improvement for 2 weeks then patient will be taken off the study
VII SERIOUS ADVERSE EVENT REPORTING
All serious events as defined in Appendix E of protocol must be reported as soon as you are aware of them to
Drs Kashif AnisZaigham Abbas at the Aga Khan University Hospital VIII EVALUATION
Evaluation before Treatment
Patient should have evaluation by gastroenterologyoncology to determine eligibility
All Patients should have
Diagnosis of hepatoma with the help of Biopsy if possible or by the help of CT Scan or Serum alpha fetoprotein level fulfilling 2 out of 3 criteria
Complete history and physical examination CBC differential platelet count serum sodium potassium glucose calcium creatinine bilirubin alkaline phosphatase AST ALT alpha fetoproteinAFP prothrombin time PT and Serum Albumin
CT scan of the abdomen with contrast Cardiac evaluation of LVEF CT scans and plain x-rays if clinically indicated
Evaluation during Chemotherapy
CBC differential platelets count sodium potassium creatinine glucose bilirubin alkaline phosphatase ASTALT
CBC should be repeated prior to every chemotherapy course
Re-evaluation of response after every 3 courses of chemotherapy would be done radio logically by repeating a CT scanx rays as indicated by sites of disease involvement
Evaluation After chemotherapy
All patients will be followed thereafter cessation of chemotherapy due to progression of disease every three to six months until a total of five years for evaluation of five-year disease free and overall survival
Evaluation of toxicity profile
This should be based either on the NCIC common toxicity criteria attached at the end or any other major toxicity criteria eg NCI and documented in the attached form
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None