|Phase III, Phase II||Biomarker/Laboratory analysis, Treatment||Active||18 and over||NCI||NCI-2011-01987|
RTOG-0848, CDR0000659092, U10CA021661, U10CA180868, NCT01013649
This randomized phase II-R/III trial studies gemcitabine hydrochloride with or without erlotinib hydrochloride followed by the same chemotherapy regimen with or without radiation therapy and capecitabine or fluorouracil in treating patients with pancreatic cancer that was removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, capecitabine, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Giving chemotherapy together with or without erlotinib hydrochloride and/or radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective when given with or without erlotinib hydrochloride and/or radiation therapy in treating pancreatic cancer.
Further Study Information
I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine (gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as compared to gemcitabine alone following R0 or R1 resection of head of pancreas adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival for such patients who are without evidence of progressive disease after 5 cycles of gemcitabine based chemotherapy. (Phase III)
I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after 5 cycles of adjuvant chemotherapy.
II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and without erlotinib for patients with resected head of pancreas adenocarcinoma.
III. To evaluate adverse events with and without erlotinib for patients with resected head of pancreas adenocarcinoma.
IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who are disease free after adjuvant chemotherapy.
V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas adenocarcinoma in order to determine the frequency with which objective criteria of resectability are present.
VI. To determine if patients reporting low baseline fatigue, as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS), and survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride orally (PO) once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. (NOTE: Phase II-R erlotinib hydrochloride randomization completed, Arm 2 closed to accrual effective 2/19/2014)
Patients with no disease progression after treatment in arm I or II are then stratified according to their first randomization treatment arm (arm I vs arm II) and randomized to 1 of 2 additional treatment arms (arm III or IV).
ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.
ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II. Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy (3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed.
After completion of study treatment, patients are followed up periodically.
- Histologic proof of primary head of pancreas invasive adenocarcinoma managed with a potentially curative resection (i.e., removal of all gross tumor) involving a classic pancreaticoduodenectomy (Whipple) or a pylorus preserving pancreaticoduodenectomy; patients with invasive adenocarcinoma that also contains a component of intraductal papillary mucinous neoplasm (IPMN) are eligible
- The operating surgeon must document in the operative note that a complete gross excision of the primary tumor was achieved; the pathology report must include documentation of the margin status and the size of the tumor; the pathology report must also include the status of the three major margins—bile duct, pancreatic parenchyma, and retroperitoneal (uncinate)
- Interval between definitive tumor-related surgery and 1st step registration between 21-70 days
- Patients will be staged according to the 6th edition American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-3, N0-1, M-0 being eligible
- Zubrod performance status 0 or 1
- Complete history and physical examination including weight and Zubrod status within 31 days of study entry
- Before starting therapy the patient should be able to maintain adequate oral nutrition of >= 1500 calories estimated caloric intake per day and be free of significant nausea and vomiting
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Hemoglobin (Hgb) >= 8.0 g/dL (transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable)
- Post resection serum cancer antigen (CA)19-9 =< 180 units/mL within 21 days of registration on study
- Serum total bilirubin =< twice the institutional upper limit of normal (ULN) within 21 days of registration on study
- Creatinine levels =< twice the institutional upper limit of normal within 21 days of registration on study
- Serum glutamic oxaloacetic transaminase (SGOT) must be =< 2.5 x institutional ULN within 21 days of registration on study
- Negative serum pregnancy test for women of childbearing potential within 14 days of study registration
- Abdominal/pelvic computed tomography (CT) scan with contrast is preferred; abdominal CT alone is acceptable only if insurance restrictions are experienced; chest CT/x-ray (CT of chest preferred) within 31 days of registration on study; patients allergic to intravenous (IV) contrast can have magnetic resonance imaging (MRI) of the abdomen/pelvis instead
- Signed study-specific informed consent
- Consultation, agreement, and documentation in the patient's chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol
- Women of childbearing potential and male participants must practice adequate contraception
- Patients with active human immunodeficiency virus (HIV) infection are eligible if their cluster of differentiation (CD)4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active antiretroviral treatment (HAART) is allowed
- Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN's that contain some secondary (minor) foci of adenocarcinoma are also not eligible
- Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy
- Prior systemic chemotherapy for pancreas cancer; note that prior chemotherapy for a different cancer is allowable
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- Previous history of invasive malignancy (except non-melanoma skin cancer) unless the patient has been disease free for at least 2 years prior to study entry (patients with a previous history of carcinoma in situ are eligible)
- 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 3 months of study registration
- 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 at the time of registration
- Pregnant or lactating women
- Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- If surgical margin status cannot be determined after consultation with the operating surgeon and the institutional pathologist, the patient will be ineligible
Trial Lead Organizations/Sponsors
National Cancer Institute
|Ross Abrams||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01013649
ClinicalTrials.gov processed this data on April 10, 2014
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