Study Stopped
Trial would not be completed in a reasonable timeframe per CTEP guidelines
High or Standard Intensity Radiation Therapy After Gemcitabine Hydrochloride and Nab-paclitaxel in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery
A Phase II Randomized Trial Evaluating the Addition of High or Standard Intensity Radiation to Gemcitabine and Nab-paclitaxel for Locally Advanced Pancreatic Cancer
5 other identifiers
interventional
20
1 country
46
Brief Summary
This randomized phase II trial studies how well high or standard intensity radiochemotherapy after gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) work compared with gemcitabine hydrochloride and nab-paclitaxel alone in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine, may make tumor cells more sensitive to radiation therapy. Giving radiation therapy in different ways and adding chemotherapy may kill more tumor cells. It is not yet known whether high intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel is more effective than standard intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel or gemcitabine hydrochloride and nab-paclitaxel alone in treating pancreatic cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Aug 2013
Typical duration for phase_2
46 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2013
CompletedFirst Submitted
Initial submission to the registry
August 9, 2013
CompletedFirst Posted
Study publicly available on registry
August 13, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2016
CompletedResults Posted
Study results publicly available
March 22, 2018
CompletedJuly 13, 2018
June 1, 2018
2.8 years
August 9, 2013
October 6, 2017
June 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival
Survival time is defined as time from randomization to date of death from any cause and was to be estimated by the Kaplan-Meier method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients last reported to be alive at time of study termination is reported.
From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.
Secondary Outcomes (3)
Overall Survival Within SMAD4 Subsets
From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.
Patterns of Failure (Local and Metastatic Failure)
From randomization until last follow-up. Maximum follow-up at time of study termination was 8.3 months.
Correlation Between SMAD4 Status Determined by Immunohistochemistry (IHC) and Genetic SMAD4 Status
Baseline
Study Arms (3)
Chemotherapy + high intensity radiation
EXPERIMENTALInduction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity
Chemotherapy + low intensity radiation
EXPERIMENTALInduction chemotherapy with four cycles of gemcitabine and nab-paclitaxel \[randomized to this arm after 3rd cycle and no progression\]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity
Chemotherapy
ACTIVE COMPARATORGemcitabine and nab-paclitaxel until progression or unacceptable toxicity \[randomized to this arm after 3rd cycle and no progression\]
Interventions
50.4 Gy in 28 1.8 Gy fractions (IMRT or 3D-CRT), 5 days/week, starting 3-5 weeks after the last dose of induction chemotherapy
825 mg/m2 PO twice daily, 5 days/week, beginning on the first day of radiation therapy and ending on the last day of radiation therapy.
1000 mg/m2 weekly as a 30 minute infusion after nab-Paclitaxel, three weeks on and 1 week off \[1 cycle = 4 weeks\]
63 Gy intensity-modulated radiation therapy (IMRT) in 28 2.25 Gy fractions, 5 days/week, starts 3-5 weeks after the last dose of induction chemotherapy
125 mg/m2 weekly as a 30-40 minute infusion, three weeks on and 1 week \[1 cycle = 4 weeks\]
Eligibility Criteria
You may qualify if:
- Histologically or cytologically proven diagnosis of adenocarcinoma of the pancreas prior to registration
- Tumor diameter ≤ 7 cm
- Unresectable by radiographic criteria (pancreas protocol CT or MRI) or exploration within 30 days prior to registration.
- A cell block or core biopsy must be submitted for central review and analysis of SMAD4 status as soon as possible following step 1 registration.
- No distant metastases, based upon the following minimum diagnostic workup:
- History/physical examination within 30 days prior to registration
- Whole body fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG-PET/CT) within 30 days prior to registration NOTE: If whole-body FDG-PET/CT is not performed, CT of the chest and CT (or MRI) of abdomen and pelvis must be obtained (imaging of abdomen and pelvis need not be repeated if already included in pancreas protocol study)
- Zubrod Performance Status 0-1 within 30 days prior to registration
- Age ≥ 18;
- Complete blood count (CBC)/differential obtained within 14 days prior to step 1 registration, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- Platelets ≥ 100,000 cells/mm3
- Hemoglobin ≥ 8.0 g/dl (NOTE: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
- Additional laboratory studies within 14 days prior to registration:
- carbohydrate antigen 19-9 (CA19-9); NOTE: in the event that a stent has been placed and biliary obstruction has been relieved, the CA19-9 should be drawn post stent placement
- +7 more criteria
You may not qualify if:
- More than one primary lesion
- Prior invasive malignancy (unless disease free for a minimum of 1095 days \[3 years\]); Non-melanomatous skin cancer and previous early prostate cancer that had a non-rising prostate-specific antigen (PSA) are eligible
- Prior systemic anti-cancer therapy for pancreatic cancer; note that prior chemotherapy for a different cancer is allowable
- Prior radiation therapy to the abdomen that would result in overlap of radiation therapy fields
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients
- Prior allergic reaction to the study drug(s) involved in this protocol
- Pre-existing Grade 2 or greater neuropathy
- Distant metastases
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Radiation Therapy Oncology Grouplead
- National Cancer Institute (NCI)collaborator
- NRG Oncologycollaborator
Study Sites (46)
Kaiser Permanente Oakland-Broadway
Oakland, California, 94611, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051, United States
Kaiser Permanente Cancer Treatment Center
South San Francisco, California, 94080, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Saint Joseph Hospital
Chicago, Illinois, 60657, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
Peoria, Illinois, 61615-7827, United States
OSF Saint Francis Medical Center
Peoria, Illinois, 61637, United States
Radiation Oncology Associates PC
Fort Wayne, Indiana, 46804, United States
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805, United States
McFarland Clinic PC-William R Bliss Cancer Center
Ames, Iowa, 50010, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995, United States
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, 56601, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
CoxHealth South Hospital
Springfield, Missouri, 65807, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
Mount Holly, New Jersey, 08060, United States
Capital Health Medical Center-Hopewell
Pennington, New Jersey, 08534, United States
University of Rochester
Rochester, New York, 14642, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Akron General Medical Center
Akron, Ohio, 44307, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010, United States
Paoli Memorial Hospital
Paoli, Pennsylvania, 19301, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Thompson Cancer Survival Center
Knoxville, Tennessee, 37916, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Intermountain Medical Center
Murray, Utah, 84157, United States
McKay-Dee Hospital Center
Ogden, Utah, 84403, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Saint Vincent Hospital
Green Bay, Wisconsin, 54301, United States
Saint Mary's Hospital
Green Bay, Wisconsin, 54303, United States
Bay Area Medical Center
Marinette, Wisconsin, 54143, United States
Door County Cancer Center
Sturgeon Bay, Wisconsin, 54235-1495, United States
Related Publications (1)
Jani A, Horowitz DP. Radiation Therapy Deviations in Trial of Locally Advanced Pancreatic Cancer [corrected]. JAMA. 2016 Oct 4;316(13):1409. doi: 10.1001/jama.2016.9778. No abstract available.
PMID: 27701653DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This study terminated early with only 20 registered (346 planned) and 13 randomized (288 planned). Follow-up forms were collected on only 3 patients.
Results Point of Contact
- Title
- Wendy Seiferheld, M.S.
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Edgar Ben-Josef
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 9, 2013
First Posted
August 13, 2013
Study Start
August 1, 2013
Primary Completion
June 1, 2016
Study Completion
June 1, 2016
Last Updated
July 13, 2018
Results First Posted
March 22, 2018
Record last verified: 2018-06