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

NCT02873598 | Completed Phase 1 Results DMC

• 1 other identifier: 16-1139.cc
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Pancreatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 months

Secondary Outcomes (6)

• Local Control

  Up to 5 years

• Progression Free Survival

  Up to 5 years

• Overall Survival

  Up to 5 years

• Small Intestine Changes

  6 weeks after SBRT

• Vascular and Cellular Changes

  6 weeks after SBRT

Study Arms (3)

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.

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

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.

Drug: FOLFIRINOX or gemcitabine/abraxane; Radiation: SBRT

Interventions

FOLFIRINOX or gemcitabine/abraxane DRUG

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

Also known as: nab-paclitaxel

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

SBRT 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 1; FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 2; FOLFIRINOX or gemcitabine/abraxane followed by SBRT Dose level 3

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Gemcitabine; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Sana Karam
• Organization: University of Colorado Cancer Center

sana.karam@cuanschutz.edu

7208480141

Study Officials

• Sana Karam, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: August 8, 2016
• First Posted: August 19, 2016
• Study Start: November 17, 2016
• Primary Completion: June 7, 2019
• Study Completion: November 28, 2022
• Last Updated: December 19, 2022
• Results First Posted: October 13, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)