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 Has Been Removed by Surgery

Brief summary public domain (ClinicalTrials.gov)

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, by stopping them from dividing, or by stopping them from spreading. 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.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: 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 based chemotherapy or non-gemcitabine based chemotherapy such as modified fluorouracil-leucovorin-irinotecan-oxaliplatin regimen (FOLFIRINOX) further enhances survival for such patients who are without evidence of progressive disease after 5 months of adjuvant chemotherapy. (Phase III) SECONDARY OBJECTIVES: 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 months 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 without disease progression after treatment in arm I or II are randomized to 1 of 2 additional treatment arms (arm III or IV). ARM I: Patients receive either gemcitabine hydrochloride or allowable combination chemotherapy per standard of care for 5 months. ARM II (closed to accrual 4/2/14): Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive the same treatment as in arm I for 1 month. ARM IV: Patients receive the same treatment as in arm I for 1 month. 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. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline. After completion of study treatment, patients are followed up every 3-6 months for up to 4 years, then yearly.

Intervention public domain (ClinicalTrials.gov)

Radiation: 3-Dimensional Conformal Radiation Therapy. Undergo 3-dimensional conformal radiation therapy

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo blood and tissue sample collection

Intervention public domain (ClinicalTrials.gov)

Drug: Capecitabine. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Chemotherapy. Given combination chemotherapy

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo CT

Intervention public domain (ClinicalTrials.gov)

Drug: Erlotinib Hydrochloride. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Fluorouracil. Given IV

Intervention public domain (ClinicalTrials.gov)

Drug: Gemcitabine Hydrochloride. Given IV

Arm public domain (ClinicalTrials.gov)

Arm I (gemcitabine hydrochloride or combination chemotherapy) (active comparator): Patients receive either gemcitabine hydrochloride or allowable combination chemotherapy per standard of care for 5 months. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.

Arm public domain (ClinicalTrials.gov)

Arm II (gemcitabine hydrochloride, erlotinib hydrochloride) (experimental): Patients receive gemcitabine hydrochloride IV over 30 minutes once a week for 3 weeks then off 1 week and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline. (closed to accrual 4/2/14)

Arm public domain (ClinicalTrials.gov)

Arm III (chemotherapy) (experimental): Patients receive the same treatment as in arm I for 1 month. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.

Arm public domain (ClinicalTrials.gov)

Arm IV (chemotherapy, chemoradiotherapy) (experimental): Patients receive the same treatment as in arm I for 1 month. 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 BID 5 days per week or fluorouracil IV continuously for 5.5 weeks or until radiotherapy is completed. Patients undergo CT, MRI, and/or x-ray imaging throughout the trial. Patients also undergo blood sample collection during screening and follow-up and undergo tissue sample collection at baseline.

Primary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) [Phase II]. Overall survival is estimated by the Kaplan-Meier method. Survival time is measured from step 1 randomization to date of death from any cause or last known follow-up (censored). Analysis was to occur after 200 deaths were reported. Time frame: From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years..

Primary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) [Phase III]. Overall survival (OS) is estimated by the Kaplan-Meier method. Survival time is measured from step 2 randomization to date of death from any cause or last known follow-up (censored). Analysis was to occur at the earlier of 316 reported deaths or when all patients have five years potential follow-up from step 2 randomization. Time frame: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization..

Secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase II]. Time frame: From step1 randomization (gemcitabine vs. gemcitabine/erlotinib) to disease event, death, or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years. Five-year rates are reported here..

Secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase III]. Time frame: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to disease event, death, or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization..

Secondary outcome public domain (ClinicalTrials.gov)

Number of Participants by Highest Grade Adverse Event Reported (Phase II). Time frame: From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years..

Secondary outcome public domain (ClinicalTrials.gov)

Number of Participants by Highest Grade Adverse Event Reported (Phase III). Time frame: From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization..

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) by Baseline Fatigue Group. Time frame: From enrollment (step 1) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 13.2 years, measured from enrollment. Two- and five-year rates are reported here..

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * 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) * For patients who have not started their chemotherapy prior to registration, the interval between definitive tumor-related surgery and 1st step registration must be between 21-70 days; for patients entering on the study who have already received up to 3 months of adjuvant chemotherapy as per the treating institution, the interval between definitive tumor-related surgery and day one of adjuvant chemotherapy must be between 21-77 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. Pathologic reporting using the College of American Pathologists (CAPS) format is strongly encouraged * Age \>= 18 * Zubrod performance status 0 or 1 * Complete history and physical examination including weight and Zubrod status within 31 days of study entry (or within 31 days prior to day 1 of chemotherapy post-surgery for those patients having started chemotherapy prior to first step registration) * 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 * Complete blood count (CBC)/differential obtained within 21 days of registration on study (or within 21 days prior to day 1 of chemotherapy post-surgery for those patients having started chemotherapy prior to first step registration) * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * Platelets \>= 100,000/mm\^3 * Hemoglobin \>= 8.0 g/dL (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable) * Post resection serum cancer antigen (CA)19-9 =\< 180 units/mL AND prior to any …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 546 participants (actual).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) [Phase II] [From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.]. Median, months (95% Confidence Interval). Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=163): 29.9 (21.7 to 33.4); Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=159): 28.1 (20.7 to 30.9). Analysis, Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) vs Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride): Hazard Ratio (HR) 1.04 (95% CI 0.79 to 1.38); p=0.62; Log Rank; superiority.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) [Phase III] [From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to the date of death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.]. Median, months (90% Confidence Interval). Arm III (Chemotherapy) (n=174): 31.1 (25.3 to 37.6); Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 27.3 (24.5 to 31.7). Analysis, Arm III (Chemotherapy) vs Arm IV (Chemotherapy, Chemoradiotherapy): Hazard Ratio (HR) 0.96 (90% CI 0.79 to 1.18); p=0.38; Log Rank; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase II] [From step1 randomization (gemcitabine vs. gemcitabine/erlotinib) to disease event, death, or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years. Five-year rates are reported here.]. Median, months (95% Confidence Interval). Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=163): 12.7 (10.8 to 15.7); Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=159): 12.4 (9.7 to 16.5). Analysis, Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) vs Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride): Hazard Ratio (HR) 1.02 (95% CI 0.80 to 1.31); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (Percentage of Participants Alive Without Disease) [Phase III] [From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to disease event, death, or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.]. Median, months (90% Confidence Interval). Arm III (Chemotherapy) (n=174): 12.4 (9.6 to 15.2); Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 15.6 (13.2 to 18.8). Analysis, Arm III (Chemotherapy) vs Arm IV (Chemotherapy, Chemoradiotherapy): Hazard Ratio (HR) 0.82 (90% CI 0.68 to 0.99); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants by Highest Grade Adverse Event Reported (Phase II) [From step 1 randomization (gemcitabine vs. gemcitabine/erlotinib) to death or last follow-up. Maximum follow-up at the time of the phase II analysis was 6.2 years.]. Count Of Participants, Participants. Grade 1: Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=160): 6; Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=158): 3. Grade 2: Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=160): 20; Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=158): 24. Grade 3: Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=160): 100; Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=158): 101. Grade 4: Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=160): 32; Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=158): 27. Grade 5: Arm I (Gemcitabine Hydrochloride or Combination Chemotherapy) (n=160): 2; Arm II (Gemcitabine Hydrochloride, Erlotinib Hydrochloride) (n=158): 3.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants by Highest Grade Adverse Event Reported (Phase III) [From step 2 randomization (chemotherapy vs. chemotherapy followed by chemoradiation) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 12.8 years, measured from step 2 randomization.]. Count Of Participants, Participants. Grade 1: Arm III (Chemotherapy) (n=174): 22; Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 16. Grade 2: Arm III (Chemotherapy) (n=174): 50; Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 56. Grade 3: Arm III (Chemotherapy) (n=174): 67; Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 79. Grade 4: Arm III (Chemotherapy) (n=174): 21; Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 23. Grade 5: Arm III (Chemotherapy) (n=174): 1; Arm IV (Chemotherapy, Chemoradiotherapy) (n=180): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (Percentage of Participants Alive) by Baseline Fatigue Group [From enrollment (step 1) to death or last follow-up. Maximum follow-up at time of the phase III analysis was 13.2 years, measured from enrollment. Two- and five-year rates are reported here.]. Number, Percentage of participants (90% Confidence Interval). Two years: High Fatigue (n=71): 54.1 (44.3 to 64.0); Low Fatigue (n=352): 58.1 (53.7 to 62.6). Five years: High Fatigue (n=71): 21.1 (13.0 to 29.5); Low Fatigue (n=352): 25.1 (21.1 to 29.1). Analysis, High Fatigue vs Low Fatigue: Hazard Ratio (HR) 0.89 (90% CI 0.71 to 1.13); p=0.21; Log Rank; superiority.