A Phase II Randomized Study of Concurrent Hyperthermia and Chemoradiotherapy vs. Chemoradiotherapy Alone Following Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer (HEATPAC)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Overall survival (at 1 year)
研究概览
简要总结
This is a phase II randomized study of concurrent chemoradiotherapy and local hyperthermia (study group) versus chemoradiotherapy alone (control group) following neoadjuvant chemotherapy in locally advanced pancreatic cancer. Each of the treatment arm would have 39 patients based on the expected overall 1 year survival advantage of +20% over the control group (p0=40%).
详细描述
This phase II randomized trial is a part of the comprehensive protocol designed for the locally advanced pancreatic cancers (LAPC). All patients of LAPC, fulfilling the following criteria of "Unresectable LAPC" would be considered to be eligible for enrolment in the study.
These include:
- Major venous infiltration / thrombosis of the portal vein or superior mesenteric vein extending for several centimeters (precluding vein resection and reconstruction)
- Tumor encasement (≥180°) of the superior mesentric artery or proximal hepatic artery
- Tumor abutment (<180°) of the celiac trunk
- Tumor invasion of the aorta
- Presence of metastasis to lymph nodes beyond the field of resection All patients would be reviewed at the Pancreas Cancer Tumor Board, University Hospital Zurich and those fulfilling the above condition/s would be considered for the study protocol of LAPC. Following a detailed work up, all eligible patients with primary tumours more than 4 cm would be considered for HEATPAC study.
Patients would be randomized by random digit using a double blinded strategy into either (a) Control group : Treated with concurrent chemoradiotherapy or (b) Study group: Treated with local hyperthermia along with concurrent chemoradiotherapy.
Treatment in both groups would be initiated with 4 cycles of neo-adjuvant chemotherapy (FOLFIRINOX). At completion of 4 cycles of neo-adjuvant FOLFIRINIOX, patients would be evaluated by PET-CT, 3-4 week following the last cycle of FOLFIRINIOX. Patients in control group would be taken up for concurrent gemcitabine (400 mg / sq.m weekly) along with loco-regional radiotherapy by SIB-IMRT to a dose of 50.4 Gy in 28 fractions. Patients in the study group would be receiving loco-regional hyperthermia to a temperature of 40-41°C, weekly for 1 hour before gemcitabine and before radiotherapy. The gemcitabine and in loco-regional radiotherapy in study group would be similar to that of the control group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of locally advanced pancreatic cancer with
- •Major venous infiltration / thrombosis of the portal vein or superior mesenteric vein extending for several centimeters
- •Tumor encasement (≥180°) of the superior mesentric artery or proximal hepatic artery
- •Tumor abutment (<180°) of the celiac trunk
- •Tumor invasion of the aorta
- •Presence of metastasis to lymph nodes beyond the field of resection
- •Histopathologically proven ductal adenocarcinoma of the pancreas (biopsy /cytology)
- •Eastern Cooperative Oncology Group (ECOG) performance scale 0 and 1
- •Age: 18 to 80 years
- •At least one of the diameters of the primary tumor or regional lymph node or both should be greater than 4 cm, as confirmed on contrast-enhanced computed tomography (CECT).
- •Patients, have primary tumor or regional lymph node or both lesser than 4 cm, as confirmed on CECT but have specific medical contraindications to stereotactic body radiation therapy or irreversible electroporation or as per patient's preference could be considered for HEATPAC.
- •No evidence of any distant metastasis
- •Patients with microscopic peritoneal carcinomatosis, detected on laparoscopy following 4 cycles on neo-adjuvant FOLFIRINOX would be included.
- •Estimated life expectancy of at least 6 months
- •Adequate kidney functionality defined as creatinine clearance >50ml/min
- •Adequate liver functionality defined as total bilirubin ≤ 2x of the upper limit of normal
- •Adequate bone marrow reserves: White blood cell count ≥ 2.5 x 10˄9/L, Platelet count ≥ 100 x 10˄9/L, Hemoglobin ≥ 8.0g/L
- •Women of child-bearing age must secure sufficient contraception control during the clinical trial and six months after the clinical trial is completed
- •For females of child bearing potential, negative pregnancy test within 2 week prior to randomization.
- •Female patients should not be lactating
- •Absence of psychological, familial, sociological or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule
排除标准
- •Histopathology other than ductal adenocarcinoma pancreas
- •Prior radiotherapy to the site of treatment
- •Patients with unequivocal distant metastasis including liver
- •Patients with gross peritoneal carcinomatosis on laparoscopy
- •No prior or concurrent malignancies other than surgically treated squamous cell or basal cell carcinoma of the skin
- •No serious medical illness which would prevent informed consent or limit survival to less than 2 years
- •Active uncontrolled bacterial, viral or fungal infections until these conditions are corrected or controlled.
- •Psychiatric or addictive disorders or other conditions that would preclude the patient from meeting the study requirements.
- •Patients having metal implants, pacemakers or clustered markers.
- •Metallic endobiliary stenting would be a contraindication, hence plastic stents may be used if biliary drainage is indicated.
- •Patient with a history of myocardial infarction within the past 12 months
- •No connective disease disorders that contraindicate radiotherapy, e.g., Scleroderma
- •Pre-existing grade 2 peripheral neuropathy
- •Any known contraindication or hypersensitivity to the chemotherapeutic agents
- •Pregnancy, lactation period or lack of reliable contraception
- •Any other disease or therapy, which, present a risk to the patient or which are not compatible with the aims of the clinical trial
- •Patients would express their inability to travel on their own to Kantonsspital Aarau, (KSA) for hyperthermia treatment
- •Indications that the person concerned will be noncompliant to the clinical trial plan because of unwillingness to cooperate or difficulties in keeping the check-up appointments
研究组 & 干预措施
Chemoradiotherapy (CTRT) (Control Group)
Intervention type:
Drug and Radiation
Intervention name:
Drug (Gemcitabine) Radiation (Loco-regional radiotherapy by SIB-IMRT)
Intervention description:
Radiotherapy: 5 days a week (Days 1 to 5) of each week for 5.5 weeks (28 fractions), Total dose: 50.4 Gy at 1.8 Gy /fr. over 5.5 weeks Chemotherapy: Gemcitabine (400 mg / sq. m) would be administered weekly 24 hours after hyperthermia on Day 2 and after radiotherapy every week on D2
干预措施: Chemoradiotherapy (CTRT) (Other)
Thermochemoradiotherapy (CTRTHT)
Intervention type:
Drug, Radiation and Hyperthermia
Intervention name:
Drug (Gemcitabine) Radiation (Loco-regional radiotherapy by SIB-IMRT) Hyperthermia (Loco-regional hyperthermia),
Intervention description:
Radiotherapy: 5 days a week (Days 1 to 5) of each week for 5.5 weeks (28 fractions), Total dose: 50.4 Gy at 1.8 Gy /fr. over 5.5 weeks Chemotherapy: Gemcitabine (400 mg / sq. m) would be administered weekly 24 hours after hyperthermia on Day 2 and after radiotherapy every week on D2 Hyperthermia: Weekly Local hyperthermia before radiotherapy on D1 of every week, 41-43°C for 60 mins, once every week
干预措施: Thermochemoradiotherapy (CTRTHT) (Other)
结局指标
主要结局
Overall survival (at 1 year)
时间窗: From date of randomization until the date of death from any cause assesed at 1 year or whichever is earlier
Overall survival
次要结局
- Progression free survival (as per Response Evaluation Criteria in Solid Tumours (RECIST), v1.1)(From date of randomization until the first docemented disease progression as evident on CECT / PET-CT / MRI as per RECIST criteria (v1.1), whichever came first assessed upto the end of study period of 60 weeks)
- Patterns of failure : both local and systemic (as per RECIST, v1.1)(From date of randomization until the disease progression either locally or at distant sites as evident on CECT / PET-CT / MRI as per RECIST criteria (v1.1), whichever came first assessed upto the end of study period of 60 weeks)
- Acute and late morbidity (as per Common Toxicity Criteria for Adverse Effects (CTCAE) v4.03)(Acute or late morbidity from date of randomization until the patients death from any cause as per the CTCAE v4.03 whichever came first assessed upto the end of study period of 60 weeks)
研究者
Prof. Dr. med. Niloy Ranjan Datta
Senior Consultant and Head, Radiation Research, Radiation Oncology
Kantonsspital Aarau