Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma

NCT01146054 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-17073SU-02012010-4843PANC0007
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 3

Brief Summary

This multi-institutional trial aims to evaluate the potential benefit and side effects of adding fractionated stereotactic body radiotherapy/surgery (SBRT) before and after chemotherapy with gemcitabine for locally advanced pancreatic cancer.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• To Determine the Rate of (Grade 2 or Greater) Gastrointestinal Toxicity Attributable to Gemcitabine and Fractionated SBRT at One Year.

  Grade 2 or greater late gastritis, fistula, enteritis, or ulcer or late grade 3-4 gastrointestinal toxicity at one year.

  One year.

Secondary Outcomes (4)

• Evaluate Acute Gastrointestinal Toxicity up to 3 Months of Treatment.

  Within 3 months of treatment.

• To Evaluate Progression Free Survival Following Gemcitabine and SBRT for up to 5 Years of Follow up .

  Up to 5 years of follow up.

• To Determine the Overall Survival in Pancreatic Cancer Patients Treated With Gemcitabine and SBRT for up to 5 Years of Follow up.

  Up to 5 years of follow up.

• Proportion of Participants Achieving Freedom From Local Progression (FFLP) in Patients Treated With Gemcitabine Followed by Fractionated Stereotactic Body Radiotherapy (SBRT) for up to 5 Years of Follow up.

  Up to 5 years of follow up.

Study Arms (1)

SBRT and Gemzar

EXPERIMENTAL

Before stereotactic Body Radiotherapy (SBRT) 3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F) - Positron emission tomography/Computerized tomography) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D (4 dimensional) pancreatic protocol CT). Patients are treated by either respiratory gated (Trilogy, Elekta, Novalis) or by respiratory tracking (CyberKnife). SBRT is delivered in 5 fractions of 6.6 Gy by LINAC-based or CyberKnife based radiotherapy over a five-day period. Gemcitabine, cycles should resume/start up to 4 weeks following SBRT on a 3-week on, 1-week off schedule. Initial follow up is at 4, 6, 9 and 12 months and then for years 2-5 is every 3-6 months.

Device: CyberKnife based stereotactic radiotherapy; Drug: Gemcitabine; Drug: Fludeoxyglucose (18F) (FDG)

Interventions

CyberKnife based stereotactic radiotherapy DEVICE

1. Initial orthogonal images will be obtained to confirm location of fiducial seeds. 2. Synchrony respiratory tracking system must be used to correct for respiratory associated tumor motion. This system utilizes a series of optical diodes placed upon the patient's chest wall. While the orthogonal images are obtained, the computer generates a model correlating the position of the chest wall with the position of the internal fiducials. This model is continuously updated during treatment to correct for subtle changes in tumor location. 3. Quality assurance will be performed as per standard practice at each participating institution.

Also known as: Trilogy(Varian, Palo Alto CA), Novalis (BrainLab, Feldkirchen, Germany), Synergy (Elekta AB, Stockholm, Sweden),

SBRT and Gemzar

Gemcitabine DRUG

Treatment calculated per the needs of each patient and given at the instruction of the investigator; iv (intravenous).

Also known as: Gemzar

SBRT and Gemzar

Fludeoxyglucose (18F) (FDG) DRUG

FDG-PET/CT scan is used in treatment planning. Treatment with 18F-FDG is calculated per the needs of each patient and given at the instruction of the investigator; iv

Also known as: fluorodeoxyglucose (18F), 18F-FDG, FDG

SBRT and Gemzar

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the pancreas.
• Unresectable disease as determined by a pancreatic cancer surgeon and assessment at a GI oncology tumor board (JHU - Johns Hopkins University, SU - Stanford University, or MSKCC - Memorial Sloan Kettering Cancer Center).
• Up to 3 weeks of gemcitabine chemotherapy is allowed prior to SBRT.
• Pancreatic tumors must be less than 7.5 cm in greatest axial dimension (or \<1000 cc in volume) at the time of treatment planning.
• No prior upper abdominal or liver radiation therapy.
• No chemotherapy within 2 weeks of radiotherapy, or chemotherapy within parameters set by Investigator for each institution.
• Age \>=18 years.
• No infections requiring systemic antibiotic treatment.
• Karnofsky \>= 70% (see Appendix III).
• Patients must have acceptable organ and marrow function as defined below (within 1 month prior to radiotherapy):
• leukocytes: \>=3,000/microliter (uL)
• absolute neutrophil count: \>=1,500uL
• platelets: \>=100,000/uL
• total bilirubin: within 1.5 times (1.5X) normal institutional limits
• AST (aspartate aminotransferase)(SGOT -Serum glutamic oxaloacetic transaminase)/ALT(alanine aminotransferase)(SGPT-serum glutamic-pyruvic transaminase): \<=2.5 X institutional upper limit of normal

You may not qualify if:

• Patients who have had prior radiotherapy to the upper abdomen.
• Patients receiving more than 1 cycle of gemcitabine chemotherapy or other therapy prior to SBRT.
• Children are excluded because pancreatic tumors rarely occur in this age group. Furthermore, treatment requires a great deal of patient cooperation including the ability to lie still for several hours in an isolated room.
• No laboratory personnel will be included.
• 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.
• Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy without evidence of disease for \> 5 years will be allowed to enter the trial.
• 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 (follicle stimulating hormone) levels greater than 35 IU/mL (international units/milliliter). A negative urine or serum pregnancy test must be obtained within 72 hours prior to the start of study medication in all women of childbearing potential. Male subjects must also agree to use effective contraception for the same period as above.

Sponsors & Collaborators

• Stanford University: lead
• Johns Hopkins University: collaborator

Study Sites (3)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Fluorodeoxyglucose F18

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; Deoxyglucose; Deoxy Sugars; Carbohydrates

Results Point of Contact

• Title: Albert C. Koong, M.D., Ph.D., Sue and Bob McCollum Professor, Associate Chair of Radiation Onocology
• Organization: Stanford University Comprehensive Cancer Center

akoong@stanford.edu

650-498-7703

Study Officials

• Albert Koong

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sue and Bob McCollum Professor

Study Record Dates

• First Submitted: June 15, 2010
• First Posted: June 17, 2010
• Study Start: October 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2015
• Last Updated: December 19, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)