E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with resected head of pancreas adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Patients with resected head of pancreas adenocarcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052747 |
E.1.2 | Term | Adenocarcinoma pancreas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) Ph II-R: To determine whether the addition of erlotinib to gemcitabine 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).
2) Ph III:To determine whether the use of concurrent fluoropyrimidine and
radiotherapy following adjuvant gemcitabine based chemotherapy further enhances
survival for such patients who are without evidence of progressive disease after 5
cycles of gemcitabine based chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
(Ph II-R, Erlotinib randomization completed, Arm 2 closed; accrual effective
04/02/2014)
To evaluate:
1) - disease-free survival (D-FS) of adjuvant chemotherapy followed by radiotherapy &concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma (RHoPA) who are D-F after 5 cycles of adjuvant chemotherapy.
2)DFS of standard adjuvant gemcitabine chemotherapy with/without erlotinib for patients with RHoPA
3) AEs with/without erlotinib for patients with RHoPA
4) AEs of adjuvant chemotherapy ± radiation therapy &concurrent fluoropyrimidine for patients withRHoPA who are D-F after adjuvant chemotherapy.
5) preoperative cross-sectional imaging of primary head of pancreas adenocarcinoma to determine frequency with which objective criteria of resectability are present.
6) To determine if patients reporting low baseline fatigue,as measured by
FACITFatigue, predicts survival& explore correlations between baseline fatigue,
as measured by PROMIS & survival. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) 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).
2) Interval between definitive tumor-related surgery and 1st step registration between 21-70 days.
3) Patients will be staged according to the 6th edition AJCC staging system with
pathologic stage T1-3, N0-1, M-0 being eligible. Pathologic reporting using the CAPS
format is strongly encouraged.
4) Age ≥ 18.
5) Zubrod performance status 0 or 1.
6) Complete history and physical examination including weight and Zubrod status
within 31 days of study entry.
7) 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.
8) CBC/differential obtained within 21 days of registration on study, 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.)
9) Post resection serum CA19-9 ≤ 180 units/mL within 21 days of registration on
study.
10) Patients must have:
- Serum total bilirubin ≤ twice the institutional upper limit of normal within 21 days of registration on study.
- Creatinine levels ≤ twice the institutional upper limit of normal within 21 days of
registration on study.
- SGOT must be ≤ 2.5 x the institutional upper limit of normal within 21 days of
registration on study.
11) Negative serum pregnancy test for women of childbearing potential within 14
days of study registration.
12) Abdominal/pelvic 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 IV contrast can have MRI of the abdomen/pelvis instead.
13) Signed study-specific informed consent.
14) Consultation, agreement, and documentation in the patient’s chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol.
15) Women of childbearing potential and male participants must practice adequate contraception.
16) Patients with active HIV infection are eligible if their CD4 count is > 499/cu mm
and their viral load is < 50 copies/ml; use of HAART is allowed. |
|
E.4 | Principal exclusion criteria |
exclusion criteria:
(conditions for patient eligibility (02 September 2014)
1) 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 intraductal papillary mucinous neoplasms (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.
2) Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy.
3) Prior systemic chemotherapy for pancreas cancer; note that prior chemotherapy
for a different cancer is allowable.
4) Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
5) 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.
6) 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
7) Pregnant or lactating women.
8) Women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic.
9) If surgical margin status cannot be determined after consultation with the
operating surgeon and the institutional pathologist, the patient will be ineligible. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Ph II-R: For the erlotinib question (first randomization closed to accrual
04FEB2014
2) Overall survival (OS) (failure: death due to any cause)
3) Ph III: For the chemoradiation question (second randomization): Overall survival (OS) (failure: death due to any cause)
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|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Ph II-R: projected analysis timeline of ~ 2.5 years from the amendment.
2) Ph III: 3 years after last patient randomized
|
|
E.5.2 | Secondary end point(s) |
For both the erlotinib question (Ph II-R) and the chemoradiation question (Ph III) unless otherwise noted: (first randomization closed to accrual):
1 Disease-free survival (failure: local or regional disease progression, distant metastases, second primary, or death due to any cause)
2 Adverse events
3 Pre-op imaging to determine frequency of objective criteria of resectability
4 Quality of Life: fatigue as measured by the FACIT-F (primary) and the PROMIS derived short form (exploratory)
5 Laboratory correlative studies related to K-Ras (first randomization only) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 1-5: 3 years after last patient randomized |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard clinical practice |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Germany |
Italy |
Spain |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis
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|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |