Pancreatic Cancer MetastaticPhase 2FOLFOX-DNCT01652976
Phase II Study of 5-FU, Oxaliplatin Plus Dasatinib in Metastatic Pancreatic Adenocarcinoma
A Phase 2 study testing Dasatinib and mFOLFOX6 in people with Pancreatic Cancer Metastatic, run by University of Florida at 1 site in United States.
Trial summary
The purpose of this research study is to determine if the study drug, dasatinib, given in combination with 5-Fluorouracil, leucovorin and oxaliplatin (FOLFOX) will work against metastatic pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer Metastatic
- What is being tested?
- Dasatinib and mFOLFOX6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Jul 2020
- 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
- Pancreatic adenocarcinoma with evidence of metastatic disease on imaging
- Measurable disease (per RECIST 1.1)
- ECOG Performance Status 0-2
- No prior chemotherapy or radiotherapy for metastatic pancreatic cancer. Patients may have received prior treatment for non-metastatic disease; however the diagnosis of metastatic disease must have been made more than 6 months after completion of treatment.
- Patients may have a history of other malignancies if there is no current evidence of persistent or recurrent disease and they are not undergoing any active therapy (including hormonal)
- Patent biliary system
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- Patients receiving anti-coagulation treatment with an agent such as Coumadin or heparin may be allowed to participate, provided they are on stable anti-coagulation therapy with no active bleeding and have no condition that carries a high risk of bleeding
- Adequate organ and marrow function
- Ability to take oral medication (dasatinib must be swallowed whole)
- Patient agrees to discontinue prohibited concomitant medications
- Age > 18 years
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception throughout the study and for at least 4 weeks after the last dose of study drug.
- A male subject of fathering potential must use an adequate method of contraception throughout the study and for at least 4 weeks after the last dose of study drug.
Who cannot join
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug. Women who are pregnant or breastfeeding and sexually active fertile men not using effective birth control if their partners are WOCBP are also excluded.
- History of known brain metastases or carcinomatous meningitis
- Recent major surgery (within 4 weeks) or minor surgery (within 2 weeks), excluding placement of a vascular access device or biliary stent
- Uncontrolled diabetes
- Any sensory neuropathy > grade 1 at baseline
- Serious active or uncontrolled infection
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- Concurrent medical condition which may increase the risk of toxicity including clinically significant pleural or pericardial effusion, patients with known DPD deficiency or patients with a history of allergic reactions attributed to oxaliplatin, 5-FU or leucovorin.
- Cardiac Symptoms including unstable angina or stable angina markedly limiting ordinary physical activity, NYHA class III or IV congestive heart failure, myocardial infarction or stroke within 6 months of study enrollment, diagnosed congenital long QT syndrome, any history of clinically significant ventricular arrhythmias, prolonged QTc interval on pre-entry ECG or clinically significant peripheral vascular disease.
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
- History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders, diagnosed acquired bleeding disorder within one year or ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.
- History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy, might affect the interpretation of the results of the study, or that puts the subject at high risk for treatment complications.
- Use of category I drugs that are generally accepted to have a risk of causing Torsades de Pointes
- Use of potent CYP3A4 inhibitors that significantly increase dasatinib exposure
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
- Inability to comply with study and/or follow-up procedures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of 5-Fluorouracil, Oxaliplatin Plus Dasatinib (FOLFOX-D) in First-line Metastatic Pancreatic Adenocarcinoma
The purpose of this research study is to determine if the study drug, dasatinib, given in combination with 5-Fluorouracil, leucovorin and oxaliplatin (FOLFOX) will work against metastatic pancreatic cancer.
Dasatinib is a Food and Drug Administration (FDA) approved drug for treating chronic myelogenous leukemia and acute lymphoblastic leukemia, however it is not currently approved for use in the treatment of pancreatic cancer.
Read the detailed description
Systemic control of pancreatic cancer remains a clinical unmet need. The recent superiority of 5-FU based combination therapies over the historical standard gemcitabine represents an opportunity to develop novel combinations of synergistic and effective cytotoxic and biologic targeted therapies. Src excess activity has been demonstrated in pancreatic cancer and is implicated in the invasive and metastatic phenotype clearly represented by this disease. Inhibition of Src activity is associated with numerous biologic modifications capable of positively modifying this phenotype and appears to have synergy with restoring inherent chemosensitivity. The addition of dasatinib to FOLFOX (FOLFOX-D) represents a novel therapeutic regimen in pancreatic cancer with safety and pharmacokinetic data already having been established in colorectal cancer. This protocol will test the safety and activity of this combination in pancreatic cancer where current clinical outcomes remain far from optimal.
- Conditions
- Pancreatic Cancer Metastatic
- Being tested
- Dasatinib, mFOLFOX6
- Keywords
- Metastatic, Pancreatic Cancer, Adenocarcinoma
- Medical subject headings
- Neoplasm Metastasis, Pancreatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel
Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle
mFOLFOX6Drug
Also called Oxaliplatin, Leucovorin, 5-Fluorouracil
mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Dasatinib and mFOLFOX6 Receives: Drug: Dasatinib; Drug: mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Determine activity of 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus dasatinib on progression free survival (PFS) in patients with metastatic pancreatic adenocarcinoma
Measured: 3 years
Secondary outcomes (10)
Response Rate
To determine the response rate (RR) by RECIST 1.1 criteria. The response rate is the number of subjects who had either a complete or partial response by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). The imaging modality used for all RECIST assessments in this study was CT.
Measured: 3 years
Freedom From Metastasis
To determine the rate of freedom from metastasis (FFM), which is defined as the percentage of subjects with documented progressive disease (by RECIST 1.1 criteria) who had no new lesions. RECIST 1.1 criteria defines progressive disease as the appearance of one or more new lesions and/or the increase of the sum of the largest diameter of the target lesions by at least 20% from the smallest sum collected (the sum must also have increased by at least 5 mm).
Measured: 3 years
Median Time To Progression
To determine the median time to progression (TTP). TTP is defined as the time (in months) from when a subject achieves either a complete or partial response by RECIST 1.1 criteria until progressive disease (by RECIST 1.1 criteria) or death occurs.
Measured: 3 years
Median Overall Survival
To determine median overall survival (OS) in months
Measured: 4 years
Clinical Benefit Rate
To determine the clinical benefit rate (CBR). The CBR is defined as the percentage of subjects who achieved either a complete or partial response or stable disease by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). By RECIST 1.1 criteria, a subject is considered to have stable disease when the sum of the largest diameter of the target lesions has neither decreased enough to qualify as a partial response not increased enough to qualify as progressive disease.
Measured: 3 years
Site of Failure
To determine the site of failure of this regimen in this population. The site of failure is the anatomical site(s) where disease progression by RECIST 1.1 criteria was noted on imaging.
Measured: 3 years
Safety and Tolerability
To determine the safety profile and tolerability of this regimen in this population by evaluating acute treatment related toxicities using CTCAE v4.0 criteria. Using the CTCAE v4.0, the severity of each adverse event reported was graded on a scale of 1 (mild severity) to 5 (fatal). For this outcome measure the percentage of subjects experiencing any adverse event of each CTCAE grade was tabulated.
Measured: 3 years
Drug Compliance
To determine patient compliance with oral therapy. For this outcome measure, compliance with oral therapy is defined as the percentage of subjects that took dasatinib for at least one cycle. Compliance with oral therapy was documented with a medication diary that subjects were asked to complete to document whether each dose of dasatinib was taken.
Measured: 3 years
Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007
To determine the quality of life (QOL) of patients receiving this therapy using the CTSQ questionnaire. The CTSQ consists of 16 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are used to calculate 3 subscores: Expectations of Therapy (ET), Feelings about Side Effects (FSE), and Satisfaction with Therapy (SWT). Each subscore is calculated by multiplying the mean response value for the questions used to calculate that subscore by 25. The maximum value is 100 and the minimum value is 0 for all 3 subscores. A higher subscore indicates better QOL in that area. The mean difference in each of the 3 subscores from baseline and 95% confidence interval for the entire study population is reported here. A negative mean difference indicates a decrease from baseline in QOL for that area.
Measured: 3 years
Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0)
The FACT-Hep consists of 45 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are summed to calculate 5 subscores: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The mean difference in each of the 5 subscores from baseline, as well as the total score of the 5 subscores (the FACT-Hep Total Score) for the entire study population is reported here. The mean difference in the FACT-G Total Score (calculated by summing the PWB, SWB, EWB, and FWB subscores) is also reported here. A negative mean difference indicates a decrease from baseline in QOL. Score ranges- PWB subscore: 0-28, SWB subscore: 0-28, EWB subscore: 0-24, FWB subscore: 0-28, HCS subscore: 0-72, FACT-G Total Score: 0-108, and FACT-Hep Total Score: 0-180. A higher value for each subscore or total score indicates better QOL.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionFeb 2018
- Study completionJul 2020
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 Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Thomas J George, Jr., MD, FACP, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01652976
- Sponsor's protocol ID
- IRB201600540
- Other IDs
- CA180-359, OCR11303
- Acronym
- FOLFOX-D
- Status last verified
- Dec 2020
- First submitted
- 23 Jul 2012
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
George TJ Jr, Trevino JG, Liu C. Src inhibition is still a relevant target in pancreatic cancer. Oncologist. 2014 Feb;19(2):211. doi: 10.1634/theoncologist.2013-0410. Epub 2014 Jan 23. No abstract available.
PubMed 24457377
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of 5-Fluorouracil, Oxaliplatin Plus Dasatinib (FOLFOX-D) in First-line Metastatic Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT01652976
- Acronym / sponsor ID
- FOLFOX-D / IRB201600540
- Conditions
- Pancreatic Cancer Metastatic
- Keywords
- Metastatic, Pancreatic Cancer, Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jul 2012 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 30 Jul 2012 (estimated)
- Results
- Posted 13 Jun 2019
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 research study is to determine if the study drug, dasatinib, given in combination with 5-Fluorouracil, leucovorin and oxaliplatin (FOLFOX) will work against metastatic pancreatic cancer.
Dasatinib is a Food and Drug Administration (FDA) approved drug for treating chronic myelogenous leukemia and acute lymphoblastic leukemia, however it is not currently approved for use in the treatment of pancreatic cancer.
Detailed description
Systemic control of pancreatic cancer remains a clinical unmet need. The recent superiority of 5-FU based combination therapies over the historical standard gemcitabine represents an opportunity to develop novel combinations of synergistic and effective cytotoxic and biologic targeted therapies. Src excess activity has been demonstrated in pancreatic cancer and is implicated in the invasive and metastatic phenotype clearly represented by this disease. Inhibition of Src activity is associated with numerous biologic modifications capable of positively modifying this phenotype and appears to have synergy with restoring inherent chemosensitivity. The addition of dasatinib to FOLFOX (FOLFOX-D) represents a novel therapeutic regimen in pancreatic cancer with safety and pharmacokinetic data already having been established in colorectal cancer. This protocol will test the safety and activity of this combination in pancreatic cancer where current clinical outcomes remain far from optimal.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Dasatinib, Drug: mFOLFOX6Dasatinib and mFOLFOX6 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Pancreatic adenocarcinoma with evidence of metastatic disease on imaging
- Measurable disease (per RECIST 1.1)
- ECOG Performance Status 0-2
- No prior chemotherapy or radiotherapy for metastatic pancreatic cancer. Patients may have received prior treatment for non-metastatic disease; however the diagnosis of metastatic disease must have been made more than 6 months after completion of treatment.
- Patients may have a history of other malignancies if there is no current evidence of persistent or recurrent disease and they are not undergoing any active therapy (including hormonal)
Key exclusion criteria (16 listed)
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug. Women who are pregnant or breastfeeding and sexually active fertile men not using effective birth control if their partners are WOCBP are also excluded.
- History of known brain metastases or carcinomatous meningitis
- Recent major surgery (within 4 weeks) or minor surgery (within 2 weeks), excluding placement of a vascular access device or biliary stent
- Uncontrolled diabetes
- Any sensory neuropathy > grade 1 at baseline
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 |
|---|---|---|
| DasatinibAlso: SprycelDasatinib 150mg PO daily on days 1-14 of each 14 day cycle | Drug | Treatment Arm |
| mFOLFOX6Also: Oxaliplatin, Leucovorin, 5-FluorouracilmFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle | Drug | Treatment Arm |
Primary outcome
Progression Free Survival (PFS)
Time frame: 3 years
Determine activity of 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus dasatinib on progression free survival (PFS) in patients with metastatic pancreatic adenocarcinoma
10 secondary outcomes
Response Rate
Time frame: 3 years
Freedom From Metastasis
Time frame: 3 years
Median Time To Progression
Time frame: 3 years
Median Overall Survival
Time frame: 4 years
Clinical Benefit Rate
Time frame: 3 years
Site of Failure
Time frame: 3 years
Safety and Tolerability
Time frame: 3 years
Drug Compliance
Time frame: 3 years
Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007
Time frame: 3 years
Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0)
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24457377George TJ Jr, Trevino JG, Liu C. Src inhibition is still a relevant target in pancreatic cancer. Oncologist. 2014 Feb;19(2):211. doi: 10.1634/theoncologist.2013-0410. Epub 2014 Jan 23. No abstract available.
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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.
Thomas J George, Jr., MD, FACP principal investigator
University of Florida
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 Dasatinib and mFOLFOX6 in people with Pancreatic Cancer Metastatic, run by University of Florida 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 5 Jan 2021. 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 13 Jun 2019). 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?
Progression Free Survival (PFS) (time frame: 3 years). 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 NCT01652976, 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 5 Jan 2021.