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

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ClinicalTrials.gov Identifier: NCT02873598
Recruitment Status : Recruiting
First Posted : August 19, 2016
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

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).

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: FOLFIRINOX or gemcitabine/abraxane Radiation: SBRT Phase 1

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) After Induction Chemotherapy for Locally Advanced Pancreatic Cancer
Actual Study Start Date : November 29, 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FOLFIRINOX or gemcitabine/abraxane followed by SBRT
SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane
Drug: FOLFIRINOX or gemcitabine/abraxane
Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.
Other Name: nab-paclitaxel

Radiation: 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.




Primary Outcome Measures :
  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. [ 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.


Secondary Outcome Measures :
  1. Local Control [ Time Frame: Up to 5 years ]
    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.

  2. Progression Free Survival [ Time Frame: Up to 5 years ]
    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.

  3. Overall Survival [ Time Frame: Up to 5 years ]
    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.

  4. Small Intestine Changes [ Time Frame: 6 weeks after SBRT ]
    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.

  5. Vascular and Cellular Changes [ Time Frame: 6 weeks after SBRT ]
    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

  6. Quality of Life (QOL) [ Time Frame: 6 months after SBRT ]
    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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02873598


Contacts
Contact: Robyn Swing 720-848-0607 ROBYN.SWING@UCDENVER.EDU

Locations
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Robyn Swing    720-848-0607    ROBYN.SWING@UCDENVER.EDU   
Principal Investigator: Karyn Goodman, MD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Karyn C Goodman, MD University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02873598     History of Changes
Other Study ID Numbers: 16-1139.cc
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:
Induction Chemotherapy
Stereotactic Body Radiotherapy (SBRT)
Dose Escalation
Locally Advanced Pancreatic Cancer (LAPC)
Maximum Tolerated Dose (MTD)

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Albumin-Bound Paclitaxel
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators