CholangiocarcinomaPhase 1/2NCT00955721
A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer
A Phase 1/2 study testing Gemcitabine, Oxaliplatin and Sorafenib in people with Cholangiocarcinoma and Biliary Tract Cancer, run by University of Miami at 1 site in United States.
Trial summary
The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there is no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma, Biliary Tract Cancer, Gallbladder Cancer
- What is being tested?
- Gemcitabine, Oxaliplatin and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jul 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- Histologically or cytologically confirmed biliary tract or gallbladder carcinoma
- Any stage of disease is allowed but the patients must not be candidates for curative resection
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 in Ph I
- ECOG performance status 0-2 in Ph II. Patients with ECOG PS of 2 will only be enrolled if they will comprise at most 25% of the total accruals. This will be monitored in real time to ensure that at any point during accrual, PS 2 patients will comprise <= 25% of the total accruals
- Patients must have normal organ and marrow function as defined below within 14 days of study entry:
Show all 18Show fewer
- Absolute neutrophil count >= 1,500 cells/mm3
- Platelet count >= 60,000/mm3
- Creatinine < 1.5 upper limit of normal (ULN).
- Aspartate transaminase (AST) and Alanine transaminase (ALT) <= 2.5 x ULN.
- Bilirubin <= 3.0 mg/dl
- International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates.
- Any number of previous lines of chemotherapy is allowed for the phase I portion
- During the phase II trial, no prior chemotherapy for inoperable or metastatic disease is allowed except 5-FU or Capecitabine as radiosensitizers. Prior adjuvant chemotherapy is allowed.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
- Life expectancy of greater than 12 weeks
Who cannot join
- Investigational agents within 28 days prior to Day 1 of study
- Chemotherapy within 4 weeks prior to Day 1 of study
- Nitrosoureas, mitomycin-C within 6 weeks prior to Day 1 of study.
- Prior treatment with sorafenib, gemcitabine or oxaliplatin
- Prior history of peripheral neuropathy > Grade 1 (e.g., diabetic neuropathy)
- Pregnant or breast-feeding female
Show all 22Show fewer
- Patients with a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to sorafenib, oxaliplatin or gemcitabine
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Known human immunodeficiency virus (HIV) infection and Hepatitis B and Hepatitis C.
- Active clinically serious infection > CTCAE Grade 2.
- Arterial thrombotic/embolic events like myocardial infarct and cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
- Use of St. John's Wort or rifampin (rifampicin).
- Any medical condition, which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of Combination of Gemcitabine, Oxaliplatin and Sorafenib (GEMOX-Sorafenib) in Patients With Advanced Biliary Tract Cancer
The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there is no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.
Read the detailed description
The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there are no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.
- Conditions
- Cholangiocarcinoma, Biliary Tract Cancer, Gallbladder Cancer
- Being tested
- Gemcitabine, Oxaliplatin, Sorafenib
- Keywords
- Cholangiocarcinoma, Biliary Tract Cancer, Gallbladder Cancer
- Medical subject headings
- Cholangiocarcinoma, Biliary Tract Neoplasms, Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
OxaliplatinDrug
Also called Eloxatin
Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
SorafenibDrug
Also called BAY 43-9006
Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: GEMOX + Sorafenib | Experimental | Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib.
* Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. Receives: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Sorafenib |
| Phase 2 - RPTD GEMOX + Sorafenib | Experimental | Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
* Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
* Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. Receives: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
Measured: First two 14-day Phase I cycles
Phase II: Obtain an Estimate of the 9-month Progression-free Survival Rate in Patients With Advanced BTC Receiving the RPTD of the Combination Sorafenib and GEMOX.
Rate of study participants achieving progression-free survival at 9 months post-initiation of study therapy at RPTD. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.
Measured: 9 Months
Secondary outcomes (4)
Phase II: Estimate Overall Response Rate and Clinical Benefit Rate.
Overall response rate [CR + PR]. Clinical Benefit Rate [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
Measured: About 9 Months
Phase II: Estimate Overall Survival
Overall survival is defined as the time elapsed from the start of treatment until death. For surviving patients, follow-up will be censored at the date of last contact.
Measured: Start of treatment until death or date of last contact
Phase II: Further Evaluate the Safety of the Proposed Combination
Rate of study participants experiencing toxicity after receiving study therapy at the recommended Phase 2 Dose (RPTD).
Measured: About 9 Months
Phase II: Explore Biomarkers of Response to the Combination
A study of the correlation between biomarker levels and response to RPTD study therapy. Blood samples for biomarker analysis are collected at baseline and on day 1 of Cycles 2 onward
Measured: Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionJul 2014
- Study completionJul 2014
Why it stopped: Lack of Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Hosein, University of Miami
- Investigators
- Peter Hosein, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00955721
- Sponsor's protocol ID
- 20090256
- Other IDs
- SCCC-2009003
- Status last verified
- Dec 2017
- First submitted
- 6 Aug 2009
- Last updated
- 3 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Combination of Gemcitabine, Oxaliplatin and Sorafenib (GEMOX-Sorafenib) in Patients With Advanced Biliary Tract Cancer
- ClinicalTrials.gov ID
- NCT00955721
- Acronym / sponsor ID
- 20090256
- Conditions
- Cholangiocarcinoma, Biliary Tract Cancer, Gallbladder Cancer
- Keywords
- Cholangiocarcinoma, Biliary Tract Cancer, Gallbladder Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Funding
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 10 Aug 2009 (estimated)
- Results
- Posted 13 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there is no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.
Detailed description
The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there are no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: GEMOX + Sorafenib | Experimental | Drug: Gemcitabine, Drug: Oxaliplatin, Drug: SorafenibGemcitabine and Oxaliplatin (GEMOX) and Sorafenib. * Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. * Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. * Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. |
| Phase 2 - RPTD GEMOX + Sorafenib | Experimental | Drug: Gemcitabine, Drug: Oxaliplatin, Drug: SorafenibRecommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib: * Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. * Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. * Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age >= 18 years
- Histologically or cytologically confirmed biliary tract or gallbladder carcinoma
- Any stage of disease is allowed but the patients must not be candidates for curative resection
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 in Ph I
- ECOG performance status 0-2 in Ph II. Patients with ECOG PS of 2 will only be enrolled if they will comprise at most 25% of the total accruals. This will be monitored in real time to ensure that at any point during accrual, PS 2 patients will comprise <= 25% of the total accruals
Key exclusion criteria (22 listed)
- Investigational agents within 28 days prior to Day 1 of study
- Chemotherapy within 4 weeks prior to Day 1 of study
- Nitrosoureas, mitomycin-C within 6 weeks prior to Day 1 of study.
- Prior treatment with sorafenib, gemcitabine or oxaliplatin
- Prior history of peripheral neuropathy > Grade 1 (e.g., diabetic neuropathy)
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 |
|---|---|---|
| GemcitabineAlso: GemzarIntravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. | Drug | Phase 1: GEMOX + Sorafenib, Phase 2 - RPTD GEMOX + Sorafenib |
| OxaliplatinAlso: EloxatinIntravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. | Drug | Phase 1: GEMOX + Sorafenib, Phase 2 - RPTD GEMOX + Sorafenib |
| SorafenibAlso: BAY 43-9006Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. | Drug | Phase 1: GEMOX + Sorafenib, Phase 2 - RPTD GEMOX + Sorafenib |
Primary outcome
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
Time frame: First two 14-day Phase I cycles
Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
Phase II: Obtain an Estimate of the 9-month Progression-free Survival Rate in Patients With Advanced BTC Receiving the RPTD of the Combination Sorafenib and GEMOX.
Time frame: 9 Months
Rate of study participants achieving progression-free survival at 9 months post-initiation of study therapy at RPTD. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.
4 secondary outcomes
Phase II: Estimate Overall Response Rate and Clinical Benefit Rate.
Time frame: About 9 Months
Phase II: Estimate Overall Survival
Time frame: Start of treatment until death or date of last contact
Phase II: Further Evaluate the Safety of the Proposed Combination
Time frame: About 9 Months
Phase II: Explore Biomarkers of Response to the Combination
Time frame: Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cholangiocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingObservational study
Liver Cancer Registry Platform
Hepatocellular Carcinoma (HCC), Cholangiocarcinoma
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.
Peter Hosein, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gemcitabine, Oxaliplatin and Sorafenib in people with Cholangiocarcinoma and Biliary Tract Cancer, run by University of Miami at 1 site in United States.
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 18 inclusion and 22 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: stopped early, as of the sponsor's last update on 3 Jan 2018. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 13 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC). (time frame: First two 14-day Phase I cycles). The study lists 2 primary outcomes in all. 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 3 Jan 2018.