Hepatocellular CarcinomaPhase 2HCCNCT00844688
Study of Sorafenib and Gemcitabine in Advanced Hepatocellular Carcinoma (HCC)
A Phase 2 study testing sorafenib and Gemcitabine in people with Hepatocellular Carcinoma, run by Combined Military Hospital, Pakistan at 1 site in Pakistan.
Trial summary
For the majority of patients, metastatic HCC is incurable and patients should be considered candidates for clinical trials when appropriate. Till recently there was no worldwide, approved local or systemic therapy for advanced HCC and the available therapies for advanced unresectable and/or metastatic HCC have limited… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- sorafenib and Gemcitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 sitePakistan
- Study dates
- Sep 2008to Dec 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Advanced Hepatocellular carcinoma
- Histologically proven
- Child-Pugh A and B
- Age > 18 years.
- ECOG Performance Status of 0 or1
- Life expectancy of at least 12 weeks.
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- Subjects with at least one uni-dimensional (for RECIST) or bi-dimensional (for WHO) measurable lesion. Lesions must be measured by CT-scan or MRI
- Adequate bone marrow, liver and renal function as assessed by the following
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count ³ 100,000/μl
- Total bilirubin < 1.5 times the upper limit of normal
- ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- Alkaline phosphatase < 4 x ULN
- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- Serum creatinine < 1.5 x upper limit of normal. (normal creatinine value: 0.8-1.2 mg/dl)
- Signed and dated informed consent before the start of specific protocol procedures.
Who cannot join
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted) or uncontrolled hypertension.
- History of HIV infection
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft however, the organ allograft may be allowed as protocol specific.
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- Patients with evidence or history of bleeding diasthesis
- Patients undergoing renal dialysis
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry.
- Excluded therapies and medications, previous and concomitant:
- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
- Major surgery within 4 weeks of start of study
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Prior exposure to the study drug.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication). Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
Trial locations and contacts
1 site in 1 country.
Pakistan1 site, 1 recruiting
- Recruiting
Combined Military Hospital
Rawalpindi, Punjab Province, 46000
Naeem Naqi, MBBS,FCPS
About this study
Official title: A Phase II Feasibility Study of Sorafenib and Gemcitabine Combination Treatment in Patients With Advanced Hepatocellular Carcinoma
For the majority of patients, metastatic HCC is incurable and patients should be considered candidates for clinical trials when appropriate. Till recently there was no worldwide, approved local or systemic therapy for advanced HCC and the available therapies for advanced unresectable and/or metastatic HCC have limited clinical values, with low response rates and little impact on the natural history of the disease. Furthermore, the toxicities associated with these agents can be severe, requiring careful patient selection, and this dramatically decreases the number of patients who may benefit from therapy. The SHARP trial established the survival benefit of Sorafenib in Advanced HCC but the results yet remain humble. The need for more effective therapies is still there.
Study Objectives
Read more
The primary objective of this phase II study is to evaluate the efficacy and safety of Sorafenib and Gemcitabine combination in patients with advanced HCC.
Safety data and limited efficacy data will be collected for this combination in the study. All Drug-Related Adverse Events, all Adverse Events NCI CTCAE Version 3.0 Grade 3 or higher, and all Serious Adverse Events regardless of causal relationship to study drugs will be recorded in this study.
Read the detailed description
Over-all Study Design
This is a non-randomized, open-label treatment protocol for patients with advanced HCC.
30 Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis with Gemcitabine 1000mg/m2 administered on day 1 \& 8 of a 4 week cycle. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached:
- Progression of disease.
- The patient is unlikely to benefit from further treatment as Judged by the Investigator.
- Intolerable toxicity of the drugs.
- Withdrawal of consent for any reason.
Dosage, administration and duration
Doses of study drugs may be delayed or reduced in case of clinically significant toxicities that are possibly, probably or definitely related to protocol therapy. Toxicities will be graded using the NCI Common Terminology Criteria Version 3.0 (see Appendix 10.6). If a patient experiences several toxicities and there are conflicting recommendations, the recommended dose adjustment that reduces the dose to the lowest level should be used. All dose modifications will follow pre-defined dose levels as indicated below for study drugs, respectively. The dose modifications of sorafenib will follow the following dose levels:
Dose level 1 (starting dose): 400 mg (2 x 200 mg) p. o. twice daily Dose level 2: 400 mg (2 x 200 mg) p. o. once daily Dose level 3: 400 mg (2 x 200 mg) p. o. once every other day If a dose reduction by more than two dose levels from the 400 mg twice daily schedule is required, the patient should be discontinued from the study treatment. Also, at the discretion of the Investigator, the dose may be re escalated to a higher dose level up to up to a maximum of 400 mg twice daily following the resolution of the Adverse Event or an improvement in the Adverse Event to a level which permits the re-escalation of the study drug.
For Gemcitabine the potentially dose limiting toxicity is myelosuppression, dose delays are allowed for Grade 3 and 4 toxicities. Growth factors will not be administered unless delay is more than 2 weeks in recovery of hematological toxicity.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- sorafenib, Gemcitabine
- Keywords
- Hepatocellular Carcinoma, Sorafenib, Gemcitabine
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenibDrug
Also called Nexavar
Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached:
- Progression of disease.
- The patient is unlikely to benefit from further treatment as Judged by the Investigator.
- Intolerable toxicity of the drugs.
- Withdrawal of consent for any reason.
GemcitabineDrug
Also called Gemzar
Patients will be treated with Gemcitabine 1000mg/m2 administered on day 1 \& 8 of a 4 week cycle. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached:
Progression of disease. The patient is unlikely to benefit from further treatment as
Judged by the Investigator.
Intolerable toxicity of the drugs. Withdrawal of consent for any reason.
| Study group | Role | What they receive |
|---|---|---|
| sorafenib/gemcitabine | Other | Not described Receives: Drug: sorafenib; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC
Measured: 4 months
Secondary outcomes (1)
Toxicity evaluation in accordance with CTCAE v3.0
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2009 (estimated)
- Study startSep 2008
- Primary completionOct 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Combined Military Hospital, Pakistan
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Investigators
- Naeem Naqi, MBBS,FCPS, Principal investigator, Consultant Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00844688
- Sponsor's protocol ID
- HCC
- Acronym
- HCC
- Status last verified
- Feb 2009
- First submitted
- 13 Feb 2009
- Last updated
- 16 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Feasibility Study of Sorafenib and Gemcitabine Combination Treatment in Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT00844688
- Acronym / sponsor ID
- HCC / HCC
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Sorafenib, Gemcitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Combined Military Hospital, PakistanUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Sep 2008
- Primary completion
- Oct 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 16 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For the majority of patients, metastatic HCC is incurable and patients should be considered candidates for clinical trials when appropriate. Till recently there was no worldwide, approved local or systemic therapy for advanced HCC and the available therapies for advanced unresectable and/or metastatic HCC have limited clinical values, with low response rates and little impact on the natural history of the disease. Furthermore, the toxicities associated with these agents can be severe, requiring careful patient selection, and this dramatically decreases the number of patients who may benefit from therapy. The SHARP trial established the survival benefit of Sorafenib in Advanced HCC but the results yet remain humble. The need for more effective therapies is still there.
Study Objectives
The primary objective of this phase II study is to evaluate the efficacy and safety of Sorafenib and Gemcitabine combination in patients with advanced HCC.
Safety data and limited efficacy data will be collected for this combination in the study. All Drug-Related Adverse Events, all Adverse Events NCI CTCAE Version 3.0 Grade 3 or higher, and all Serious Adverse Events regardless of causal relationship to study drugs will be recorded in this study.
Detailed description
Over-all Study Design
This is a non-randomized, open-label treatment protocol for patients with advanced HCC.
30 Patients will be treated with 400 mg oral sorafenib twice a day on a continuous basis with Gemcitabine 1000mg/m2 administered on day 1 \& 8 of a 4 week cycle. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached:
- Progression of disease.
- The patient is unlikely to benefit from further treatment as Judged by the Investigator.
- Intolerable toxicity of the drugs.
- Withdrawal of consent for any reason.
Dosage, administration and duration
Doses of study drugs may be delayed or reduced in case of clinically significant toxicities that are possibly, probably or definitely related to protocol therapy. Toxicities will be graded using the NCI Common Terminology Criteria Version 3.0 (see Appendix 10.6). If a patient experiences several toxicities and there are conflicting recommendations, the recommended dose adjustment that reduces the dose to the lowest level should be used. All dose modifications will follow pre-defined dose levels as indicated below for study drugs, respectively. The dose modifications of sorafenib will follow the following dose levels:
Dose level 1 (starting dose): 400 mg (2 x 200 mg) p. o. twice daily Dose level 2: 400 mg (2 x 200 mg) p. o. once daily Dose level 3: 400 mg (2 x 200 mg) p. o. once every other day If a dose reduction by more than two dose levels from the 400 mg twice daily schedule is required, the patient should be discontinued from the study treatment. Also, at the discretion of the Investigator, the dose may be re escalated to a higher dose level up to up to a maximum of 400 mg twice daily following the resolution of the Adverse Event or an improvement in the Adverse Event to a level which permits the re-escalation of the study drug.
For Gemcitabine the potentially dose limiting toxicity is myelosuppression, dose delays are allowed for Grade 3 and 4 toxicities. Growth factors will not be administered unless delay is more than 2 weeks in recovery of hematological toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sorafenib/gemcitabine | Other | Drug: sorafenib, Drug: Gemcitabine |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- Advanced Hepatocellular carcinoma
- Histologically proven
- Child-Pugh A and B
- Age > 18 years.
- ECOG Performance Status of 0 or1
Key exclusion criteria (17 listed)
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted) or uncontrolled hypertension.
- History of HIV infection
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sorafenibAlso: NexavarPatients will be treated with 400 mg oral sorafenib twice a day on a continuous basis. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached: 1. Progression of disease. 2. The patient is unlikely to benefit from further treatment as Judged by the Investigator. 3. Intolerable toxicity of the drugs. 4. Withdrawal of consent for any reason. | Drug | sorafenib/gemcitabine |
| GemcitabineAlso: GemzarPatients will be treated with Gemcitabine 1000mg/m2 administered on day 1 \& 8 of a 4 week cycle. Patients in this protocol may continue to be treated with this combination for a minimum of 4 cycles until any of the following criteria for protocol discontinuation is reached: Progression of disease. The patient is unlikely to benefit from further treatment as Judged by the Investigator. Intolerable toxicity of the drugs. Withdrawal of consent for any reason. | Drug | sorafenib/gemcitabine |
Primary outcome
RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC
Time frame: 4 months
1 secondary outcome
Toxicity evaluation in accordance with CTCAE v3.0
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naeem Naqi, MBBS,FCPS principal investigator
Consultant Oncologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sorafenib and Gemcitabine in people with Hepatocellular Carcinoma, run by Combined Military Hospital, Pakistan at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Naeem Naqi, MBBS,FCPS (00923008435646, naqi60@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RECIST criteria for response evaluation by CT sacan abdomen in Target lesion of HCC (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2009.