Refractory Solid TumorsPhase 1Gem/DsatNCT00598091
A Phase I/Expansion Study of Dasatinib
A Phase 1 study testing gemcitabine and dasatinib in people with Refractory Solid Tumors and Pancreatic Adenocarcinoma, run by Duke University at 3 sites in United States.
Trial summary
The purpose of this study is to find the highest dose of the drugs gemcitabine and dasatinib that can be given for the treatment of pancreatic cancer. Gemcitabine (also called Gemzar™)is a drug that is given intravenously. Dasatinib (also called Sprycel™) is a tablet and will be taken by mouth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Solid Tumors, Pancreatic Adenocarcinoma
- What is being tested?
- gemcitabine and dasatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2007to May 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligibility Criteria Specific for Dose Escalation Phase
- Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include gemcitabine or for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1.
- Eligibly Criteria Specific for Expansion Phase at Recommended Phase II Dose
- Histologically or cytologically documented adenocarcinoma of the pancreas.
- Metastatic pancreatic cancer as documented by radiologic study or surgical evidence of metastatic disease.
Show all 22Show fewer
- No prior chemotherapy for metastatic pancreatic disease. Patients may have received a radiosensiting dose of 5-fluorouracil or capecitabine or other agents used as radiosensitizers with concurrent radiation therapy.
- Last dose of adjuvant chemotherapy must be at least 4 weeks prior to day 1 of the study drug treatment
- Prior radiation therapy is allowed. prior to day 1 of the study drug treatment. At least 4 weeks must have elapsed to baseline or grade 1.
- No prior treatment with gemcitabine or dasatinib in the adjuvant or metastatic setting.
- Prior gemcitabine only allowed if the gemcitabine was administered in the adjuvant setting and > 6 months has elapsed between diagnosis of metastatic disease and last gemcitabine treatment.
- No history for other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, 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 day 1 of the study drug treatment. .
- Eligibility Criteria for All Subjects
- Age >18 years.
- Karnofsky performance status >70%.
- Life expectancy of at least 3 months.
- Ability to understand and the willingness to sign a written informed consent document.
- Must meet lab requirements as defined in the protocol
- Patients should be capable of taking oral medications for prolonged compliance.
- Sexually active women of childbearing potential must use an effective method of birth control.
- All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product.
- Pregnant and/or lactating women will be excluded from this study.
Who cannot join
- Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within 28 days prior to day 1 of the study drug treatment. Patients receiving hormonal therapy for metastatic prostate or breast cancer may continue hormonal therapy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of the study drug treatment
- Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device within 7 days prior to expected start of treatment.
- Patients who have received any other investigational agents within the 28 days prior to day 1 of the study drug treatment.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption
- History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to day 1 of the study drug treatment.
Show all 24Show fewer
- History of stroke or transient ischemic attack within 6 months prior to day of the study drug treatment.
- Uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class II or greater
- Known cardiomyopathy with decreased ejection fraction (less than institutional normal limits)
- Diagnosed or congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Prolonged QTc interval on pre-study electrocardiogram (> 450 msec)
- Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the previous 6 months of day 1 of the study drug treatment
- Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks prior to day 1 of the study drug treatment
- History of significant bleeding disorder unrelated to cancer
- Medications that inhibit platelet function
- Fluid retention (i.e. pleural effusion, ascites, edema) grade > 2.
- A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
- Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
- Patients actively taking inhibitors or inducers of CYP3A4
- Patients actively taking proton pump inhibitors or H2 antagonists
- Other concurrent severe and/or poorly controlled medical condition that could compromise safety of treatment
- Any psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results.
- Patients unwilling to or unable to comply with the protocol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UNC Lineberger, Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Duke University Medical Center
Durham, North Carolina, 27710
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina
About this study
Official title: A Phase I Study of the Combination of Gemcitabine Plus Dasatinib in Patients With Refractory Solid Tumors With an Expanded Cohort in Advanced Pancreatic Cancer
The purpose of this study is to find the highest dose of the drugs gemcitabine and dasatinib that can be given for the treatment of pancreatic cancer. Gemcitabine (also called Gemzar™)is a drug that is given intravenously. Dasatinib (also called Sprycel™) is a tablet and will be taken by mouth.
Gemcitabine is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast, lung and pancreatic cancer. Dasatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia or for patients that are resistant to imatinib mesylate (Gleevec™ ).
This study will try to find the highest doses of these drugs that can be tolerated when taken in combination. The study will also look at how the drugs work in the body, and will see if there is any effect on pancreatic cancer.
Read the detailed description
This open-label, multicenter, non-randomized phase I trial of gemcitabine plus once and twice daily dasatinib is designed to assess the safety, tolerability, maximum tolerated dose/recommended phase II dose, and preliminary efficacy of this combination in adult patients with advanced solid tumors and with previously untreated metastatic pancreatic cancer. Patients will be accrued at Duke University Medical Center, the Duke Oncology Network, the University of North Carolina at Chapel Hill and Wake Forest Baptist Medical Center
Patients will be accrued to either of the gemcitabine/dasatinib arms in alternating sequential order. In the case where there is an open slot on a particular arm but not the alternative, the enrolled patient will be assigned to that open slot. For example, at the start of the trial, patient #1 will be treated on the gemcitabine with dasatinib twice daily dosing arm, patient #2 on the gemcitabine with dasatinib once daily dosing arm, patient #3 on the gemcitabine with dasatinib twice daily dosing arm, and so on. However, if, due to cohort expansion there is a slot available on one treatment arm but not the other, the patient will be accrued to the open slot.
Additionally, if one arm is held, delayed, or not pursued, accrual to the alternate arm may continue. Patients and their treating physicians will not be able to choose on their own which treatment arm that patient will be assigned to. This enrollment procedure will be the procedure for the entire trial.
For the dose escalation portion of the trial, patients will only be accrued at Duke University Medical Center. For the expanded cohort portion of patients with previously untreated metastatic pancreatic cancer treated at the recommended phase II dose of each arm, patients may be accrued at Duke University Medical Center,and the sites listed above.
NOTE: The first stage closed as of December 2008. Subjects will only be enrolled into the second stage of the this study.
- Toxicity will be assessed every visit, and as clinically indicated.
- Dose limiting toxicities will be assessed during cycle 1.
- Efficacy will be assessed every 2 cycles, and as clinically indicated.
- Plasma biomarkers will be assessed at baseline and at every restaging.
- Tissue based biomarkers (tumor and granulation tissue) will be assessed in up to 15 patients treated at Duke only. Tissue biopsy sets (a 4mm "stimulus" biopsy and a 5mm "granulation" tissue biopsy, both in the same location) will also be done both pre-treatment and on-treatment. Pre-treatment biopsies will be done on days -7 and 1, respectively. On-treatment biopsies will be done on days 1 and 8, respectively.
- Conditions
- Refractory Solid Tumors, Pancreatic Adenocarcinoma
- Being tested
- gemcitabine, dasatinib
- Keywords
- Solid Tumors, Phase I, Expanded Cohort, Pancreatic Cancer, Dasatinib, Gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemcitabineDrug
Also called Gemzar
1000mg/m2, Days 1, 8, 15
dasatinibDrug
Also called Sprycel
50mg, PO, QD
gemcitabineDrug
Also called Gemzar
1000mg/m2, days 1, 8, 15
dasatinibDrug
Also called Sprycel
50mg, PO, BID
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Not described Receives: Drug: gemcitabine; Drug: dasatinib |
| B | Active comparator | Not described Receives: Drug: gemcitabine; Drug: dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD/Recommended Phase II Dose (RPTD) of gemcitabine plus dasatinib once daily and twice daily dosing in patients with advanced solid tumors
Measured: Phase I portion of the study
Secondary outcomes (4)
To describe any dose limiting toxicities for these regimens
Measured: Every 28 days or as clinically indicated
To describe and non-dose limiting toxicities for these regimens
Measured: Every 28 days or as clinically indicated
To preliminarily describe markers of efficacy for gemcitabine plus dasatinib in patients with previously untreated metastatic pancreatic cancer: response rate, progression free survival, overall survival.
Measured: Every 8 weeks
To preliminarily describe changes in blood and urine based biomarkers,at baseline compared to first restaging and at progression, for patients with previously untreated metastatic pancreatic cancer treated on the expanded cohorts at the MTD/RPTD.
Measured: baseline, first restaging, progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2008 (estimated)
- Study startApr 2007
- Primary completionJun 2010
- Study completionMay 2012
Why it stopped: Low accrual, unable to meet endpoint in timely manner
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Solid TumorsStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Hope C Uronis, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00598091
- Sponsor's protocol ID
- Pro00012976
- Other IDs
- 9335
- Acronym
- Gem/Dsat
- Status last verified
- Nov 2012
- First submitted
- 26 Dec 2007
- Last updated
- 7 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Combination of Gemcitabine Plus Dasatinib in Patients With Refractory Solid Tumors With an Expanded Cohort in Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00598091
- Acronym / sponsor ID
- Gem/Dsat / Pro00012976
- Conditions
- Refractory Solid Tumors, Pancreatic Adenocarcinoma
- Keywords
- Solid Tumors, Phase I, Expanded Cohort, Pancreatic Cancer, Dasatinib, Gemcitabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual, unable to meet endpoint in timely manner
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Apr 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 18 Jan 2008 (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 find the highest dose of the drugs gemcitabine and dasatinib that can be given for the treatment of pancreatic cancer. Gemcitabine (also called Gemzar™)is a drug that is given intravenously. Dasatinib (also called Sprycel™) is a tablet and will be taken by mouth.
Gemcitabine is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast, lung and pancreatic cancer. Dasatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia or for patients that are resistant to imatinib mesylate (Gleevec™ ).
This study will try to find the highest doses of these drugs that can be tolerated when taken in combination. The study will also look at how the drugs work in the body, and will see if there is any effect on pancreatic cancer.
Detailed description
This open-label, multicenter, non-randomized phase I trial of gemcitabine plus once and twice daily dasatinib is designed to assess the safety, tolerability, maximum tolerated dose/recommended phase II dose, and preliminary efficacy of this combination in adult patients with advanced solid tumors and with previously untreated metastatic pancreatic cancer. Patients will be accrued at Duke University Medical Center, the Duke Oncology Network, the University of North Carolina at Chapel Hill and Wake Forest Baptist Medical Center
Patients will be accrued to either of the gemcitabine/dasatinib arms in alternating sequential order. In the case where there is an open slot on a particular arm but not the alternative, the enrolled patient will be assigned to that open slot. For example, at the start of the trial, patient #1 will be treated on the gemcitabine with dasatinib twice daily dosing arm, patient #2 on the gemcitabine with dasatinib once daily dosing arm, patient #3 on the gemcitabine with dasatinib twice daily dosing arm, and so on. However, if, due to cohort expansion there is a slot available on one treatment arm but not the other, the patient will be accrued to the open slot.
Additionally, if one arm is held, delayed, or not pursued, accrual to the alternate arm may continue. Patients and their treating physicians will not be able to choose on their own which treatment arm that patient will be assigned to. This enrollment procedure will be the procedure for the entire trial.
For the dose escalation portion of the trial, patients will only be accrued at Duke University Medical Center. For the expanded cohort portion of patients with previously untreated metastatic pancreatic cancer treated at the recommended phase II dose of each arm, patients may be accrued at Duke University Medical Center,and the sites listed above.
NOTE: The first stage closed as of December 2008. Subjects will only be enrolled into the second stage of the this study.
- Toxicity will be assessed every visit, and as clinically indicated.
- Dose limiting toxicities will be assessed during cycle 1.
- Efficacy will be assessed every 2 cycles, and as clinically indicated.
- Plasma biomarkers will be assessed at baseline and at every restaging.
- Tissue based biomarkers (tumor and granulation tissue) will be assessed in up to 15 patients treated at Duke only. Tissue biopsy sets (a 4mm "stimulus" biopsy and a 5mm "granulation" tissue biopsy, both in the same location) will also be done both pre-treatment and on-treatment. Pre-treatment biopsies will be done on days -7 and 1, respectively. On-treatment biopsies will be done on days 1 and 8, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: gemcitabine, Drug: dasatinib |
| B | Active comparator | Drug: gemcitabine, Drug: dasatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Eligibility Criteria Specific for Dose Escalation Phase
- Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include gemcitabine or for which standard curative or palliative measures do not exist or are no longer effective.
- Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1.
- Eligibly Criteria Specific for Expansion Phase at Recommended Phase II Dose
- Histologically or cytologically documented adenocarcinoma of the pancreas.
Key exclusion criteria (24 listed)
- Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within 28 days prior to day 1 of the study drug treatment. Patients receiving hormonal therapy for metastatic prostate or breast cancer may continue hormonal therapy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of the study drug treatment
- Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device within 7 days prior to expected start of treatment.
- Patients who have received any other investigational agents within the 28 days prior to day 1 of the study drug treatment.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption
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: Gemzar1000mg/m2, Days 1, 8, 15 | Drug | A |
| dasatinibAlso: Sprycel50mg, PO, QD | Drug | A |
| gemcitabineAlso: Gemzar1000mg/m2, days 1, 8, 15 | Drug | B |
| dasatinibAlso: Sprycel50mg, PO, BID | Drug | B |
Primary outcome
To determine the MTD/Recommended Phase II Dose (RPTD) of gemcitabine plus dasatinib once daily and twice daily dosing in patients with advanced solid tumors
Time frame: Phase I portion of the study
4 secondary outcomes
To describe any dose limiting toxicities for these regimens
Time frame: Every 28 days or as clinically indicated
To describe and non-dose limiting toxicities for these regimens
Time frame: Every 28 days or as clinically indicated
To preliminarily describe markers of efficacy for gemcitabine plus dasatinib in patients with previously untreated metastatic pancreatic cancer: response rate, progression free survival, overall survival.
Time frame: Every 8 weeks
To preliminarily describe changes in blood and urine based biomarkers,at baseline compared to first restaging and at progression, for patients with previously untreated metastatic pancreatic cancer treated on the expanded cohorts at the MTD/RPTD.
Time frame: baseline, first restaging, progression
Results and safety
The study was stopped early (reason given: Low accrual, unable to meet endpoint in timely manner). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2015.
Related trials for Refractory Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Solid Tumor, Advanced Solid Tumor
Active, not recruitingPhase 2
Testing MLN0128 (TAK-228) as Potentially Targeted Treatment in Cancers With TSC1 or TSC2 Genetic Changes (MATCH - Subprotocol M)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Hope C Uronis, MD principal investigator
Duke University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing gemcitabine and dasatinib in people with Refractory Solid Tumors and Pancreatic Adenocarcinoma, run by Duke University at 3 sites 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 22 inclusion and 24 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 7 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 was stopped early (reason given: Low accrual, unable to meet endpoint in timely manner). Results are not available in the source record.
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?
To determine the MTD/Recommended Phase II Dose (RPTD) of gemcitabine plus dasatinib once daily and twice daily dosing in patients with advanced solid tumors (time frame: Phase I portion of the study). 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 7 Sep 2015.