Pancreatic CancerPhase 1NCT02873598
A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
A Phase 1 study testing FOLFIRINOX or gemcitabine/abraxane and SBRT in people with Pancreatic Cancer, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This is a dose escalation trial to evaluate the safety of stereotactic body radiotherapy (SBRT) delivered in 3 fractions for patients with locally advanced pancreatic cancer (LAPC) who have received induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- FOLFIRINOX or gemcitabine/abraxane and SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2016to 28 Nov 2022
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytopathologically confirmed adenocarcinoma of the pancreas.
- Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of >180° (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement.
- No evidence of distant metastasis either prior to or after induction chemotherapy.
- Completion of at least 3 months, but no more than 6 months of standard induction chemotherapy for LAPC, which may include FOLFIRINOX or gemcitabine and nab-paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks.
- Pancreatic tumor size ≤ 5 cm.
- Age ≥18 years.
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- ECOG 0-1.
- Patients must have acceptable organ and marrow function as defined below:
- Leukocytes >3,000/µL
- Absolute neutrophil count >1,500/µL
- Platelets >70,000/µL
- Total bilirubin Within 2 x upper limit of normal
- AST (SGOT)/ALT (SGPT) <2.5 x institutional upper limit of normal
- Creatinine Within 1.5 x upper limit of normal OR
- Creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal
- Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to <= 5mm.
- Ability to understand and the willingness to sign a written informed consent document.
- Residual or on-going ≥ Grade 3 treatment-related toxicity from previous chemotherapy
Who cannot join
- Patients who have had prior abdominal radiotherapy.
- Patients receiving any investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Contraindication to IV contrast
- Patients in which iodine contrast is contraindicated.
- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. This applies to any woman who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum FSH levels greater than 35 mIU/mL. A negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential. Male subjects must also agree to use effective contraception for the same period as above.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
This is a dose escalation trial to evaluate the safety of stereotactic body radiotherapy (SBRT) delivered in 3 fractions for patients with locally advanced pancreatic cancer (LAPC) who have received induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel).
Read the detailed description
This is a phase I study, with an expansion cohort, of up to 34 patients to identify the maximum tolerated dose (MTD) of a 3-fraction regimen of stereotactic body radiotherapy (SBRT) for locally-advanced pancreatic cancer patients who have not developed distant progression following induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel) as per standard of care. After completion of induction chemotherapy, stereotactic body radiotherapy SBRT will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
- Conditions
- Pancreatic Cancer
- Being tested
- FOLFIRINOX or gemcitabine/abraxane, SBRT
- Keywords
- Induction Chemotherapy, Stereotactic Body Radiotherapy (SBRT), Dose Escalation, Locally Advanced Pancreatic Cancer (LAPC), Maximum Tolerated Dose (MTD)
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFIRINOX or gemcitabine/abraxaneDrug
Also called nab-paclitaxel
Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.
SBRTRadiation
After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 1 | Experimental | SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1- 9 Gy x 3 fractions. Receives: Drug: FOLFIRINOX or gemcitabine/abraxane; Radiation: SBRT |
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2 | Experimental | SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 -10 Gy x 3 fractions Receives: Drug: FOLFIRINOX or gemcitabine/abraxane; Radiation: SBRT |
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3 | Experimental | SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 11 Gy x 3 fractions. Receives: Drug: FOLFIRINOX or gemcitabine/abraxane; Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies.
This will be accomplished by the standard 3+3 dose escalation design. Dose limiting toxicities (DLT) are defined by ≥ Grade 3 treatment-related GI toxicity within 3 months of SBRT. These include: (1) Bowel (includes bowel perforation, obstruction, or hemorrhage) and (2) Stomach (bleeding ulcer, perforation) as determined by imaging or endoscopic evaluation.
Measured: Up to 3 months
Secondary outcomes (6)
Local Control
Local control (LC) will be measured from completion of SBRT to the time of identification of any local progression by imaging or surgical exploration. The pattern of patients experiencing local, distant or local with distant failure will be estimated using competing risks method.
Measured: Up to 5 years
Progression Free Survival
Progression free survival (PFS) will be measured from completion of SBRT to the time of tumor progression or death due to any cause. PFS will be estimated using the method of Kaplan and Meier.
Measured: Up to 5 years
Overall Survival
Overall survival (OS) will be measured from completion of SBRT until death due to any cause. OS will be estimated using the method of Kaplan and Meier.
Measured: Up to 5 years
Small Intestine Changes
Investigators will measure changes in the perfusion/permeability related parameters of peripancreatic small intestine before, during and after SBRT for patients using pCT and correlating these changes with the development of gastrointestinal toxicity such as duodenal ulcers, strictures, or enteritis. Patients will undergo baseline, post-first-fraction SBRT and post-treatment CT scans.
Measured: 6 weeks after SBRT
Vascular and Cellular Changes
Investigators will measure changes in diffusion and perfusion/permeability by using perfusion CT derived parameters that can predict treatment response and to assess any correlation between these perfusion CT derived parameters and local control and progression-free survival
Measured: 6 weeks after SBRT
Quality of Life (QOL)
The primary objective of the QOL study is to document the patient's experience of treatment for locally advanced pancreatic cancer by examining global QOL, physical symptoms, physical functioning and emotional well-being at baseline, during treatment, and after treatment. QOL measures including EORTC-QLQ-C30 questionnaire and the Pancreatic Cancer subscale (EORTC-PAN26) will be assessed 14 days prior to SBRT (Time 0), 10-12 weeks after SBRT (Time 1), and 6 months after SBRT (Time 2). The primary QOL endpoints include the EORTC global QOL, physical symptoms, physical functioning and emotional well-being.
Measured: 6 months after SBRT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2016 (estimated)
- Study start17 Nov 2016
- Primary completion7 Jun 2019
- Study completion28 Nov 2022
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 Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Sequential
- Model description
- Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sana Karam, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02873598
- Sponsor's protocol ID
- 16-1139.cc
- Status last verified
- Dec 2022
- First submitted
- 8 Aug 2016
- Last updated
- 19 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT02873598
- Acronym / sponsor ID
- 16-1139.cc
- Conditions
- Pancreatic Cancer
- Keywords
- Induction Chemotherapy, Stereotactic Body Radiotherapy (SBRT), Dose Escalation, Locally Advanced Pancreatic Cancer (LAPC), Maximum Tolerated Dose (MTD)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 17 Nov 2016 (actual)
- Primary completion
- 7 Jun 2019 (actual)
- Study completion
- 28 Nov 2022 (actual)
- First posted
- 19 Aug 2016 (estimated)
- Results
- Posted 13 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a dose escalation trial to evaluate the safety of stereotactic body radiotherapy (SBRT) delivered in 3 fractions for patients with locally advanced pancreatic cancer (LAPC) who have received induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel).
Detailed description
This is a phase I study, with an expansion cohort, of up to 34 patients to identify the maximum tolerated dose (MTD) of a 3-fraction regimen of stereotactic body radiotherapy (SBRT) for locally-advanced pancreatic cancer patients who have not developed distant progression following induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel) as per standard of care. After completion of induction chemotherapy, stereotactic body radiotherapy SBRT will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
| Arm | Type | Receives |
|---|---|---|
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 1 | Experimental | Drug: FOLFIRINOX or gemcitabine/abraxane, Radiation: SBRTSBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1- 9 Gy x 3 fractions. |
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2 | Experimental | Drug: FOLFIRINOX or gemcitabine/abraxane, Radiation: SBRTSBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 -10 Gy x 3 fractions |
| FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3 | Experimental | Drug: FOLFIRINOX or gemcitabine/abraxane, Radiation: SBRTSBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 11 Gy x 3 fractions. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically or cytopathologically confirmed adenocarcinoma of the pancreas.
- Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of >180° (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement.
- No evidence of distant metastasis either prior to or after induction chemotherapy.
- Completion of at least 3 months, but no more than 6 months of standard induction chemotherapy for LAPC, which may include FOLFIRINOX or gemcitabine and nab-paclitaxel, preferably within 2-4 weeks but no longer than 8 weeks.
- Pancreatic tumor size ≤ 5 cm.
Key exclusion criteria (6 listed)
- Patients who have had prior abdominal radiotherapy.
- Patients receiving any investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Contraindication to IV contrast
- Patients in which iodine contrast is contraindicated.
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 |
|---|---|---|
| FOLFIRINOX or gemcitabine/abraxaneAlso: nab-paclitaxelPatients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. | Drug | FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 1, FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2, FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3 |
| SBRTAfter completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions. | Radiation | FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 1, FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2, FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3 |
Primary outcome
The Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies.
Time frame: Up to 3 months
This will be accomplished by the standard 3+3 dose escalation design. Dose limiting toxicities (DLT) are defined by ≥ Grade 3 treatment-related GI toxicity within 3 months of SBRT. These include: (1) Bowel (includes bowel perforation, obstruction, or hemorrhage) and (2) Stomach (bleeding ulcer, perforation) as determined by imaging or endoscopic evaluation.
6 secondary outcomes
Local Control
Time frame: Up to 5 years
Progression Free Survival
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Small Intestine Changes
Time frame: 6 weeks after SBRT
Vascular and Cellular Changes
Time frame: 6 weeks after SBRT
Quality of Life (QOL)
Time frame: 6 months after SBRT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Sana Karam, MD principal investigator
University of Colorado, Denver
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 FOLFIRINOX or gemcitabine/abraxane and SBRT in people with Pancreatic Cancer, run by University of Colorado, Denver 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 6 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 Dec 2022. 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?
Yes. Results are posted in the registry (first posted 13 Oct 2022). 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 Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies. (time frame: Up to 3 months). 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 19 Dec 2022.