Pancreatic CancerPhase 2NCT01661114
A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
A Phase 2 study testing Gemcitabine, 5-FU and Cisplatin in people with Pancreatic Cancer and Biliary Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers leading to responses in a substantial minority and increasing survival. The use of the FOLFIRINOX regimen is limited by its' intensity and toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Biliary Cancer
- What is being tested?
- Gemcitabine, 5-FU and Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Mar 2016
- Phase
- Phase 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
- Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma or biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder carcinoma).
- Patients must have clinical/radiologic evidence of metastatic disease.
- Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin. Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
- ECOG (Eastern Cooperative Oncology Group) performance status < 1 (A measure of quality of life where 0 represents asymptomatic and 5 represents death).
- Patients must have adequate bone marrow (absolute neutrophil count >1,500/mm3, platelet count >100,000/mm3) and renal function (serum creatinine < 1.25 x ULN).
- Patients must have at least one measurable lesion per RECIST criteria.
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- Patients must be free of serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.
- Previous malignancies are permitted provided that they have been treated with curative intent and patient is without evidence of active systemic disease.
- Patients must be informed of the investigational nature of this study and provide written informed consent prior to receiving protocol treatment.
Who cannot join
- Patients with pre-existing peripheral neuropathy > grade 2 are ineligible.
- Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin.
- Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
- Serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers leading to responses in a substantial minority and increasing survival. The use of the FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical experience within the University of Michigan Pancreatic Program leads to an expectation of tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative to FOLFIRINOX include:
- Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at least as good as irinotecan (probably better, especially when delivered by FDR [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea, nausea/emesis, myelosuppression and alopecia.
- Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression, mucositis and diarrhea.
- Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold aggravated dysesthesia.
Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the investigators believe this treatment may be more widely applicable to pancreatic-biliary cancer patients, including those with advanced disease as well as being considered for use in locally advanced and neo- and adjuvant settings.
Read the detailed description
Gemcitabine combined with 5FU may enhance the activity of 5-FU in vivo. Gemcitabine is an inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides, and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is likely that concomitant administration of gemcitabine and 5FU results in increased cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and 5-FU potentiate the activity of cisplatin. These interactions underlie the clinical synergism that has been observed with platinum/5FU and platinum/gemcitabine combinations.
- Conditions
- Pancreatic Cancer, Biliary Cancer
- Being tested
- Gemcitabine, 5-FU, Cisplatin
- Keywords
- Gemcitabine, Infusional 5-Fluorouracil,Cisplatin, Advanced Pancreatic and Biliary Cancers, untreated & previously treated pancreatic & biliary cancer.
- Medical subject headings
- Pancreatic Neoplasms, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
5-FUDrug
Also called 5-Fluorouracil
CisplatinDrug
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine, 5-FU and Cisplatin | Experimental | 4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity Receives: Drug: Gemcitabine; Drug: 5-FU; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment
The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients.
Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 28 days
Secondary outcomes (1)
Median Overall Survival of Previously Treated and Previously Untreated Patients
To assess the overall survival following treatment with gemcitabine, 5-FU and cisplatin.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startJul 2011
- Primary completionDec 2014
- Study completionMar 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Zalupski, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661114
- Sponsor's protocol ID
- UMCC 2011.036
- Other IDs
- HUM 49518
- Status last verified
- Sep 2016
- First submitted
- 24 Jul 2012
- Last updated
- 19 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Colucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Gemcitabine, Infusional 5-Fluorouracil and Cisplatin for Advanced Pancreatic and Biliary Cancers
- ClinicalTrials.gov ID
- NCT01661114
- Acronym / sponsor ID
- UMCC 2011.036
- Conditions
- Pancreatic Cancer, Biliary Cancer
- Keywords
- Gemcitabine, Infusional 5-Fluorouracil,Cisplatin, Advanced Pancreatic and Biliary Cancers, untreated & previously treated pancreatic & biliary cancer.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Posted 4 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers leading to responses in a substantial minority and increasing survival. The use of the FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical experience within the University of Michigan Pancreatic Program leads to an expectation of tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative to FOLFIRINOX include:
- Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at least as good as irinotecan (probably better, especially when delivered by FDR [fixed-dose rate] infusion) and gemcitabine is much better tolerated with less diarrhea, nausea/emesis, myelosuppression and alopecia.
- Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression, mucositis and diarrhea.
- Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold aggravated dysesthesia.
Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the investigators believe this treatment may be more widely applicable to pancreatic-biliary cancer patients, including those with advanced disease as well as being considered for use in locally advanced and neo- and adjuvant settings.
Detailed description
Gemcitabine combined with 5FU may enhance the activity of 5-FU in vivo. Gemcitabine is an inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides, and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is likely that concomitant administration of gemcitabine and 5FU results in increased cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and 5-FU potentiate the activity of cisplatin. These interactions underlie the clinical synergism that has been observed with platinum/5FU and platinum/gemcitabine combinations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine, 5-FU and Cisplatin | Experimental | Drug: Gemcitabine, Drug: 5-FU, Drug: Cisplatin4 cycles - Gemcitabine, 5-FU and Cisplatin (2 months)-Continue treatment until progression of disease or intolerable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma or biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder carcinoma).
- Patients must have clinical/radiologic evidence of metastatic disease.
- Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin. Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
- ECOG (Eastern Cooperative Oncology Group) performance status < 1 (A measure of quality of life where 0 represents asymptomatic and 5 represents death).
- Patients must have adequate bone marrow (absolute neutrophil count >1,500/mm3, platelet count >100,000/mm3) and renal function (serum creatinine < 1.25 x ULN).
Key exclusion criteria (4 listed)
- Patients with pre-existing peripheral neuropathy > grade 2 are ineligible.
- Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin.
- Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents.
- Serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.
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 |
|---|---|---|
| Gemcitabine | Drug | Gemcitabine, 5-FU and Cisplatin |
| 5-FUAlso: 5-Fluorouracil | Drug | Gemcitabine, 5-FU and Cisplatin |
| Cisplatin | Drug | Gemcitabine, 5-FU and Cisplatin |
Primary outcome
The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment
Time frame: 28 days
The primary objective of this clinical trial is to estimate the response rate to treatment with the triplet chemotherapy regimen of gemcitabine, infusional 5-FU, and cisplatin, in untreated and previously treated advanced pancreatic and biliary cancer patients. Partial Response (PR) is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
1 secondary outcome
Median Overall Survival of Previously Treated and Previously Untreated Patients
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundColucci et al., 2002, Louvet et al., 2005, Berlin et al., 2002, Cunningham et al., 2009, Heinemann et al., 2008, Valle et al., 2010
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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.
Mark Zalupski, MD principal investigator
University of Michigan Rogel Cancer Center
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 Gemcitabine, 5-FU and Cisplatin in people with Pancreatic Cancer and Biliary Cancer, run by University of Michigan Rogel Cancer Center 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 9 inclusion and 4 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 19 Oct 2016. 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 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 4 Feb 2016). 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?
The Percentage of Untreated and Previously Treated Patients That Had a Partial Response to Treatment (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01661114, which also lists 1 linked publication.
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 19 Oct 2016.