Colorectal Liver MetastasesPhase 1NCT00557557
Safety Study of Oxaliplatin and 5-fluorouracil Followed by FUDR for Unresectable Colorectal Liver Metastases
A Phase 1 study testing Drug: 5-FU and Drug: Oxaliplatin in people with Colorectal Liver Metastases, run by David Bartlett at 1 site in United States.
Trial summary
The purpose of this study is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU in combination with Oxaliplatin delivered via isolated hepatic perfusion. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Liver Metastases
- What is being tested?
- Drug: 5-FU and Drug: Oxaliplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Aug 2014
- Phase
- Phase 1
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically proven measurable metastatic colorectal cancer limited to the parenchyma of the liver by preoperative radiological studies. Limited resectable extrahepatic disease is acceptable if the liver is felt to be the dominate site of life threatening disease.
- No chemotherapy, radiotherapy, or biologic therapy for their malignancy in the 4 weeks prior to the liver perfusion and must have recovered from all side effects.
- An ECOG performance standard of 0, 1 or 2 for 24 hours prior to surgery.
- Adequate hepatic function as evidenced by bilirubin < 2.0 mg/dL and a PT < 2 seconds greater than the upper limit of normal.
- Age equal to 18 years or older and greater than 30 kg.
- Platelet counts greater than 100,000, a hematocrit > 27.0, a white blood count > 3000/µl, Absolute neutrophil count > 1,500/μL and a creatinine less than or equal to 1.5 mg/dL or a creatinine clearance of > 60 mL/min. Patients with elevations in hepatic transaminases secondary to the presence of metastatic disease in the liver are eligible.
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- Adequate hepatic function as evidenced by:
- Serum total bilirubin < 1.5 mg/dL
- Alkaline phosphatase < 5X the ULN
- SGOT/SGPT < 5X the ULN
- Aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks and willing to sign an informed consent.
- The disease in the liver must be considered unresectable as defined by greater than three sites of disease in the liver, bilobar disease, and tumor abutting major vascular or ductal structures making anatomic resection with preservation of liver function impossible.
- Patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication
Who cannot join
- Pregnant patients and nursing mothers will be excluded due to the unknown effects of oxaliplatin on the fetus or newborn.
- Patients with active CNS metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for >3 weeks are eligible for the trial.
- Patients taking immunosuppressive drugs or on chronic anticoagulation will not be eligible.
- Patients with active infections or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment are not eligible.
- Patients with biopsy proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices on endoscopy, or radiologic studies showing significant collateral vessels around the organs drained by the portal venous system will be excluded.
- Patients with ischemic cardiac disease or history of congestive heart failure with an LVEF < 40% will be excluded.
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- Patients with COPD or other chronic pulmonary disease with PFTs indicating an FEV< 50% predicted for age will be excluded.
- Patients with a history of veno-occlusive disease of the liver are ineligible.
- History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry.
- Patients with known hypersensitivity to any of the components of oxaliplatin (or combination drug, if any).
- Patients who received radiotherapy to more than 25% of their bone marrow; or patients who received any radiotherapy within 4 weeks of entry.
- Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication).
- Peripheral neuropathy ≥ Grade 2.
- Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
- History of allogeneic transplant.
- Known HIV or Hepatitis B or C (active, previously treated or both).
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Cancer Centers Network
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase I Trial of Isolated Hepatic Perfusion With Oxaliplatin and 5-fluorouracil (5-FU) Followed by Hepatic Arterial Infusion of FUDR for Patients With Unresectable Colorectal Liver Metastases
The purpose of this study is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU in combination with Oxaliplatin delivered via isolated hepatic perfusion.
Read the detailed description
Subjects who are planning to undergo surgery for placement of HAI therapy pump will be considered for enrollment. Standard HAI therapy requires a laparotomy and placement of an intrahepatic arterial catheter that is connected to one of several commercially available subcutaneous electronic pumps. The pump is then used to deliver FUDR directly to the liver, usually beginning four weeks after surgery and lasts on average for a period of six to twelve months after the study. Current HAI therapy regimens often alternate FUDR with systemic chemotherapy. This study will examine the addition of a one hour isolated hepatic perfusion with 5-FU and Oxaliplatin prior to this standard treatment. Subjects will be given the consent form to review and after sufficient time to review the information, interested subjects will have the opportunity to ask questions of the investigators. Subjects interested in enrolling in the trial will then sign informed consent and clinical data will be collected from their chart to ensure that they meet eligibility requirements. The study will consist of a one hour isolated liver perfusion that will be performed at the time of the laparotomy to place the HAI therapy pump. Following surgery subjects will be monitored in the ICU for 24-48 hours and potentially in the hospital for an additional 5-7 days. Subjects will be free to start standard HAI therapy regimens four to six weeks following surgery. The duration of treatment, dose of HAI therapy and the decision to combine HAI with systemic chemotherapy will be at the discretion of the treating physician.
- Conditions
- Colorectal Liver Metastases
- Being tested
- Drug: 5-FU, Drug: Oxaliplatin
- Keywords
- Colorectal, liver, cancer, metastases
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: 5-FUDrug
Dose escalation (200 to 900 mg/m²) scheme, one hour isolated hepatic perfusion prior to standard treatment.
Drug: OxaliplatinDrug
40 mg/m², one hour isolated hepatic perfusion prior to standard treatment.
| Study group | Role | What they receive |
|---|---|---|
| IHP with Oxaliplatin and 5-Fluorouracil (5-FU) | Experimental | Isolated Hepatic Perfusion with Oxaliplatin and 5-Fluorouracil (5-FU) Receives: Drug: Drug: 5-FU; Drug: Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU delivered with 40mg/m² of Oxaliplatin via IHP.
Measured: 24 to 48 hours
Secondary outcomes (1)
Secondary endpoints will be to determine the response rate and survival after IHP with 5-FU and Oxaliplatin.
Measured: 3 to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2007 (estimated)
- Study startJul 2007
- Primary completionMar 2012
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Liver MetastasesStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Bartlett
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, David Bartlett, University of Pittsburgh
- Investigators
- Herbert J. Zeh, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00557557
- Sponsor's protocol ID
- 05-096
- Other IDs
- 1R21CA115059-01A1
- Status last verified
- Dec 2015
- First submitted
- 13 Nov 2007
- Last updated
- 28 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Isolated Hepatic Perfusion With Oxaliplatin and 5-fluorouracil (5-FU) Followed by Hepatic Arterial Infusion of FUDR for Patients With Unresectable Colorectal Liver Metastases
- ClinicalTrials.gov ID
- NCT00557557
- Acronym / sponsor ID
- 05-096
- Conditions
- Colorectal Liver Metastases
- Keywords
- Colorectal, liver, cancer, metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- David BartlettUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- Jul 2007
- Primary completion
- Mar 2012 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 14 Nov 2007 (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.
The purpose of this study is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU in combination with Oxaliplatin delivered via isolated hepatic perfusion.
Detailed description
Subjects who are planning to undergo surgery for placement of HAI therapy pump will be considered for enrollment. Standard HAI therapy requires a laparotomy and placement of an intrahepatic arterial catheter that is connected to one of several commercially available subcutaneous electronic pumps. The pump is then used to deliver FUDR directly to the liver, usually beginning four weeks after surgery and lasts on average for a period of six to twelve months after the study. Current HAI therapy regimens often alternate FUDR with systemic chemotherapy. This study will examine the addition of a one hour isolated hepatic perfusion with 5-FU and Oxaliplatin prior to this standard treatment. Subjects will be given the consent form to review and after sufficient time to review the information, interested subjects will have the opportunity to ask questions of the investigators. Subjects interested in enrolling in the trial will then sign informed consent and clinical data will be collected from their chart to ensure that they meet eligibility requirements. The study will consist of a one hour isolated liver perfusion that will be performed at the time of the laparotomy to place the HAI therapy pump. Following surgery subjects will be monitored in the ICU for 24-48 hours and potentially in the hospital for an additional 5-7 days. Subjects will be free to start standard HAI therapy regimens four to six weeks following surgery. The duration of treatment, dose of HAI therapy and the decision to combine HAI with systemic chemotherapy will be at the discretion of the treating physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IHP with Oxaliplatin and 5-Fluorouracil (5-FU) | Experimental | Drug: Drug: 5-FU, Drug: Drug: OxaliplatinIsolated Hepatic Perfusion with Oxaliplatin and 5-Fluorouracil (5-FU) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically proven measurable metastatic colorectal cancer limited to the parenchyma of the liver by preoperative radiological studies. Limited resectable extrahepatic disease is acceptable if the liver is felt to be the dominate site of life threatening disease.
- No chemotherapy, radiotherapy, or biologic therapy for their malignancy in the 4 weeks prior to the liver perfusion and must have recovered from all side effects.
- An ECOG performance standard of 0, 1 or 2 for 24 hours prior to surgery.
- Adequate hepatic function as evidenced by bilirubin < 2.0 mg/dL and a PT < 2 seconds greater than the upper limit of normal.
- Age equal to 18 years or older and greater than 30 kg.
Key exclusion criteria (16 listed)
- Pregnant patients and nursing mothers will be excluded due to the unknown effects of oxaliplatin on the fetus or newborn.
- Patients with active CNS metastases. Patients with stable CNS disease, who have undergone radiotherapy at least 4 weeks prior to the planned first protocol treatment and who have been on a stable dose of corticosteroids for >3 weeks are eligible for the trial.
- Patients taking immunosuppressive drugs or on chronic anticoagulation will not be eligible.
- Patients with active infections or with a fever > 101.30 F within 3 days of the first scheduled day of protocol treatment are not eligible.
- Patients with biopsy proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices on endoscopy, or radiologic studies showing significant collateral vessels around the organs drained by the portal venous system will be excluded.
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 |
|---|---|---|
| Drug: 5-FUDose escalation (200 to 900 mg/m²) scheme, one hour isolated hepatic perfusion prior to standard treatment. | Drug | IHP with Oxaliplatin and 5-Fluorouracil (5-FU) |
| Drug: Oxaliplatin40 mg/m², one hour isolated hepatic perfusion prior to standard treatment. | Drug | IHP with Oxaliplatin and 5-Fluorouracil (5-FU) |
Primary outcome
Primary endpoint is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU delivered with 40mg/m² of Oxaliplatin via IHP.
Time frame: 24 to 48 hours
1 secondary outcome
Secondary endpoints will be to determine the response rate and survival after IHP with 5-FU and Oxaliplatin.
Time frame: 3 to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2015.
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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.
Herbert J. Zeh, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Drug: 5-FU and Drug: Oxaliplatin in people with Colorectal Liver Metastases, run by David Bartlett 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 13 inclusion and 16 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: finished, as of the sponsor's last update on 28 Dec 2015. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Primary endpoint is to determine the maximum tolerated dose and dose limiting toxicity of 5-FU delivered with 40mg/m² of Oxaliplatin via IHP. (time frame: 24 to 48 hours). 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 28 Dec 2015.