Phase I/II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Grade 3-5 Toxicity Rate [Phase II]
研究概览
简要总结
The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.
详细描述
OBJECTIVES:
Primary
- Phase I: To determine the feasibility and tolerability of radiation therapy for pancreatic cancer delivered with high dose external beam radiation in a one week accelerated schedule with concurrent capecitabine
- Phase II: To demonstrate a grade 3 or greater (any) toxicity rate of less than 20%
Secondary
- To determine local control and recurrence patterns of pancreatic cancer relative to a standard regimen of 50.4 Gy as seen in historical controls
- To determine the pathologic response rate
- To determine the progression-free survival
- To determine the surgical morbidity
- To determine 30-day post-operative mortality after pancreatic resection
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to treatment.
- •No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI with gadolinium and/or manganese), and all patients must be staged with a physical exam, chest CT, and abdominal CT with intravenous contrast.
- •Only potentially resectable patients are eligible. Potentially resectable is defined as: a)no extrapancreatic disease, b)no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, and c)no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence.
- •18 years of age or older
- •ECOG Performance status of 0 or 1
- •Women of child bearing potential must practice adequate contraception and to refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment
- •Lab values as specified in the protocol
排除标准
- •Patients cannot have hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation
- •Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, or ongoing infection as manifested by fever
- •Pregnant or lactating women
- •Life expectancy < 3 months
- •Serious, uncontrolled, concurrent infection(s)
- •Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor
- •Treatment for other cancers within the last five years, except cured non-melanoma skin cancer and treated in situ cervical cancer
- •Clinically significant cardiac disease or myocardial infarction within the last 12 months
- •Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
- •Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
- •Known, existing uncontrolled coagulopathy
- •Unwillingness to participate or inability to comply with the protocol for the duration of the study
- •Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier)
- •Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency
- •Participation in any investigational drug study within 4 weeks preceding the start of study treatment
- •History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
- •Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
- •Patients should not be on cimetidine as it can decrease the clearance of 5-FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry
研究组 & 干预措施
Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 1, a total dose of 30 Gy in 10 fractions (3 Gy/day) was prescribed to the 95% isodose and administered 5 days per week over 12 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Neoadjuvant Short-Course Photon Radiation (Radiation)
Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 1, a total dose of 30 Gy in 10 fractions (3 Gy/day) was prescribed to the 95% isodose and administered 5 days per week over 12 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Capecitabine (Drug)
Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 2, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 11 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Neoadjuvant Short-Course Photon Radiation (Radiation)
Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 2, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 11 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Capecitabine (Drug)
Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 3, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 5 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Neoadjuvant Short-Course Photon Radiation (Radiation)
Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
At dose level 3, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 5 days.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Capecitabine (Drug)
All Phase I: Photon Rad+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
All Phase I participants received the radiation regimen according to the established dose escalation schedule.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Neoadjuvant Short-Course Photon Radiation (Radiation)
All Phase I: Photon Rad+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
All Phase I participants received the radiation regimen according to the established dose escalation schedule.
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Capecitabine (Drug)
Phase II: Photon Rad (MTD)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
Phase II participants received the radiation regimen established in the Phase I study (MTD).
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Neoadjuvant Short-Course Photon Radiation (Radiation)
Phase II: Photon Rad (MTD)+Capecitabine
Neoadjuvant Short-Course Photon Radiation:
Phase II participants received the radiation regimen established in the Phase I study (MTD).
Chemotherapy:
Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.
Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Grade 3-5 Toxicity Rate [Phase II]
时间窗: within 3 weeks of the start of chemoradiation therapy
All Grade 3-5 events based on CTCAEv3 related to the accelerated dose (attribution possible, probable, definite) as reported on case report forms.
Dose Limiting Toxicity (DLT) [Phase I]
时间窗: within 3 weeks of the start of chemoradiation therapy
DLT occurring within 3 weeks of the start of chemoradiation therapy was defined as: Grade 3 non-hematologic or hematologic toxicity requiring interruption of \>7 days (d) of chemo or \>3d chemoradiation; Grade 4 non-hematologic; Grade 4 neutropenia or thrombocytopenia; Treatment-related death; Delays in surgery \>3 weeks due to treatment-related toxicity. A 30% increase in any surgical complication rate beyond those previously established rates (readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%, major intra-abdominal bleeding requiring return to OR: 1.6%, delayed gastric emptying: 4.4%, and superficial wound infection rate: 8%) was also considered a DLT.
Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]
时间窗: within 3 weeks of the start of chemoradiation therapy
Neoadjuvant short-course photon radiation therapy MTD in combination with capecitabine 825 mg/m2 orally BID for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If none of 3 initial patients or only 1 of 6 patients have a DLT on dose level 3 then 6 additional patients are treated at this dose. If during this expansion, the rate of DLT exceeds 30% then the next lower dose level is declared the MTD. If no DLTs are observed, the MTD is not reached.
次要结局
- Pathologic Response Rate [Phase II](Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy)
- Progression-Free Survival (PFS) [Phase II](Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.)
- Surgical Morbidity Rate [Phase II](Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy)
- Surgical Mortality Rate [Phase II](Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy)
- Local Recurrence Rate [Phase II](Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.)
研究者
Harvey Mamon, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute