A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer

NCT ID: NCT02873598

Last Updated: 2022-12-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-17

Study Completion Date

2022-11-28

Brief Summary

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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

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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

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Pancreatic Cancer

Keywords

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Induction Chemotherapy Stereotactic Body Radiotherapy (SBRT) Dose Escalation Locally Advanced Pancreatic Cancer (LAPC) Maximum Tolerated Dose (MTD)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 1

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.

Group Type EXPERIMENTAL

FOLFIRINOX or gemcitabine/abraxane

Intervention Type DRUG

Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.

SBRT

Intervention Type RADIATION

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.

FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2

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

Group Type EXPERIMENTAL

FOLFIRINOX or gemcitabine/abraxane

Intervention Type DRUG

Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.

SBRT

Intervention Type RADIATION

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.

FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3

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.

Group Type EXPERIMENTAL

FOLFIRINOX or gemcitabine/abraxane

Intervention Type DRUG

Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.

SBRT

Intervention Type RADIATION

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.

Interventions

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FOLFIRINOX or gemcitabine/abraxane

Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.

Intervention Type DRUG

SBRT

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.

Intervention Type RADIATION

Other Intervention Names

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nab-paclitaxel

Eligibility Criteria

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Inclusion Criteria

1. Histologically or cytopathologically confirmed adenocarcinoma of the pancreas.
2. 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.
3. No evidence of distant metastasis either prior to or after induction chemotherapy.
4. 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.
5. Pancreatic tumor size ≤ 5 cm.
6. Age ≥18 years.
7. ECOG 0-1.
8. 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
9. 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.
10. Ability to understand and the willingness to sign a written informed consent document.
11. Residual or on-going ≥ Grade 3 treatment-related toxicity from previous chemotherapy

Exclusion Criteria

1. Patients who have had prior abdominal radiotherapy.
2. Patients receiving any investigational agents.
3. 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.
4. Contraindication to IV contrast
5. Patients in which iodine contrast is contraindicated.
6. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sana Karam, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado

Aurora, Colorado, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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16-1139.cc

Identifier Type: -

Identifier Source: org_study_id