A Prospective Study of Concurrent Hyperthermia, Chemotherapy and Radiotherapy in Borderline and Locally Advanced Pancreatic Cancer (PANHEAT) (PANHEAT)
A Prospective Study of Concurrent Hyperthermia Plus Standard of Care in Borderline and Locally Advanced Pancreatic Cancer (PANHEAT)
The project proposes a prospective multicenter study to evaluate the incorporation of deep regional hyperthermia into the standard of care neoadjuvant chemotherapy (mFOLFIRINOX/NABPACLITAXEL) followed by radiotherapy in borderline and locally advanced ductal adenocarcinoma pancreatic cancer. Although current treatments, based on induction chemotherapy followed by surgery or radiotherapy in selected patients, have improved survival and resection rates, overall survival remains poor.
Hyperthermia is a therapeutic intensification strategy with a solid biological basis. By controlling tumor heating (39-43°C), it enhances the efficacy of chemotherapy and radiation therapy by improving tumor oxygenation, increasing perfusion, and inhibiting DNA damage repair, without adding significant systemic toxicity. The available clinical evidence, although based mainly on retrospective and small studies, suggests that the combination of HRP with multimodal treatments improves local control, favors conversion to surgery, and may prolong survival while maintaining a favorable safety profile.
The protocol contemplates the initial administration of induction chemotherapy (preferably mFOLFIRINOX or, alternatively, gemcitabine with nab-paclitaxel)plus hyperthermia followed by multidisciplinary reevaluation. Patients who deemed resectable will undergo surgery and adjuvant chemoradiotherapy and hyperthermia. Patients without metastatic progression who remain unresectable will receive SBRT in five fractions along with sessions of deep regional hyperthermia. Subsequently, the possibility of surgery will be assessed again and a standardized follow-up will be carried out with clinical, radiological, biochemical and pathological evaluation when appropriate.
The main objective of the study is to determine the impact of this strategy on overall survival. Secondary objectives will be to evaluate progression-free survival, local control, conversion rate to surgery, proportion of R0 resections, tumor response, safety, tolerability, and feasibility of treatment. With this, the study aims to provide prospective evidence on the role of hyperthermia as a therapeutic intensification strategy in localized pancreatic cancer.
Descripción general del estudio
Estado
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Pedro C Lara, MD, PhD
- Número de teléfono: +34928012800
- Correo electrónico: plara@ufpcanarias.es
Ubicaciones de estudio
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Las Palmas
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Las Palmas de Gran Canaria, Las Palmas, España, 35010
- Hospital Universitario de Gran Canaria Dr Negrín
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Contacto:
- Laura Ferrera-Alayón, MD, Phd
- Número de teléfono: +34928450000
- Correo electrónico: lferala@gobiernodecanarias.org
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Malaga
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Málaga, Malaga, España
- Hospital Universitario Quirón Salud
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Contacto:
- Jorge Contreras, MD, PhD
- Número de teléfono: +34 951 94 00 00
- Correo electrónico: jorgecontrerasmartinez@gmail.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Patients of borderline or Locally advanced pancreatic cancer
Histopathologically proven ductal adenocarcinoma of the pancreas (biopsy/cytology).
ECOG performance scale 0 and 1.
Age between 18 and 80 years.
Adequate kidney functionality defined as creatinine clearance >50 ml/min.
Adequate liver functionality defined as total bilirubin ≤2 times of the upper limit of normal.
Adequate bone marrow reserves: WBC count ≥2.5 × 109/L, platelet count ≥100 × 109/L, hemoglobin ≥8.0 g/L.
Women of child-bearing age must secure sufficient contraception control (dual protection with condoms and pills) during the clinical trial and 6 months after the clinical trial is completed.
For females of child bearing potential, pregnancy test within 2 week prior to randomization should be negative.
Absence of psychological, familial, sociological or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule.
Exclusion criteria
Absence of distant metastasis or gross peritoneal carcinomatosis.
Prior or concurrent malignancies.
Patients having metal implants, pacemakers or clustered markers.
Patients with metallic endobiliary stent would need to be replaced with plastic stents.
Any history of myocardial infarction within the past 12 months.
Any connective tissue disorder that contraindicate RT, e.g., scleroderma.
Pre-existing grade 2 peripheral neuropathy.
Any known contraindication or hypersensitivity to the chemotherapeutic agents used in the study as decided by the medical oncologists.
Pregnancy, lactation period or lack of reliable contraception.
Any other disease or therapy, which, according to the investigator, present a risk to the patient or which are not compatible with the aims of the clinical trial.
Indications that the person concerned will possibly not keep to the clinical trial plan because of unwillingness to cooperate or difficulties in keeping the check-up appointments.
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Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Hyperthermia plus neoadjuvant chemotherapy/radiotherapy
Hyperthermia plus neoadjuvant chemotherapy (mFOLFIRINOX/nab Paclitaxel) followed by a) surgically resectable: Hyperthermia plus adjuvant chenmotherapy+/-radiotherapy b) surgically non-resectable: hyperthermia plus SBRT |
Hyperthermia plus neoadjuvant chemotherapy/radiotherapy Arm Description: Hyperthermia plus neoadjuvant chemotherapy (mFOLFIRINOX/nab Paclitaxel) followed by a) surgically resectable: Hyperthermia plus adjuvant chenmotherapy+/-radiotherapy b) surgically non-resectable: hyperthermia plus SBRT |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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overall survival
Periodo de tiempo: one year
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Time from included in the study to death for any cause |
one year
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Progression Free Survival
Periodo de tiempo: one year
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Time from included in the study to disease progression |
one year
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Objective response rate (ORR)
Periodo de tiempo: 6 months
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according to RECIST 1.1. |
6 months
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disease control rate (DCR),
Periodo de tiempo: 6 months
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according to RECIST 1.1. |
6 months
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Biochemical response using CEA and CA 19-9.
Periodo de tiempo: 6 months
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Modifications CEA and CA19.9 values |
6 months
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Conversion rate to surgery.
Periodo de tiempo: 6 months
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Resectabiity after neoadjuvant treatment |
6 months
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R0 resection rate
Periodo de tiempo: 7 months
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Rate of complete resection in surgically treated patients |
7 months
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Pathological response, including ypTNM and GRT.
Periodo de tiempo: 7 months
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Pathological confirmed response after neoadjuvant treatment |
7 months
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Local progression-free survival as first cause of failure
Periodo de tiempo: one year
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Time from included in the study to local progression after treatment as first site of failure |
one year
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Acute and late toxicity chemotherapy and radiotherapy
Periodo de tiempo: Acute: one month. Late: 12 months
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Acute and late toxicity of treatment according to CTCAE v5.0. |
Acute: one month. Late: 12 months
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Pedro C Lara, Md, PhD, Universidad Fernando Pessoa Canarias
Publicaciones y enlaces útiles
Publicaciones Generales
- Issels RD, Boeck S, Pelzer U, Mansmann U, Ghadjar P, Lindner LH, Albertsmeier M, Angele MK, Schmidt M, Xu Y, Bahra M, Pratschke J, Schoenberg M, Thasler WE, Salat C, Stoetzer OJ, Knoefel WT, Graf D, Wessalowski R, Keitel-Anselmino V, Koenigsrainer A, Bitzer M, Zips D, Bamberg M, Fietkau R, Ott O, Kawecki M, Wyrwicz L, Rutkowski P, Rentsch M, Ababei J, Reichardt P, Rigamonti M, Weber B, Abdel-Rahman S, Tschoep-Lechner K, Jauch KW, Bruns CJ, Oettle H, von Bergwelt-Baildon M, Heinemann V, Werner J; European Society for Hyperthermic Oncology (ESHO) and the German Arbeitsgemeinschaft Internistische Onkologie (AIO) Study Group for Pancreatic Cancer. Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial. Eur J Cancer. 2023 Mar;181:155-165. doi: 10.1016/j.ejca.2022.12.009. Epub 2022 Dec 30.
- Datta NR, Pestalozzi B, Clavien PA, Siebenhuner A, Puric E, Khan S, Mamot C, Riesterer O, Knuchel J, Reiner CS, Bodis S; members of the HEATPAC Trial Group. "HEATPAC" - a phase II randomized study of concurrent thermochemoradiotherapy versus chemoradiotherapy alone in locally advanced pancreatic cancer. Radiat Oncol. 2017 Nov 21;12(1):183. doi: 10.1186/s13014-017-0923-8.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del sistema endocrino
- Heridas y Lesiones
- Neoplasias por sitio
- Neoplasias
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Neoplasias de glándulas endocrinas
- Enfermedades pancreáticas
- Cambios de temperatura corporal
- Trastornos de estrés por calor
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Hipertermia
- Neoplasias pancreáticas
- Terapéutica
- Hipertermia, inducida
- Terapia de modalidad combinada
- Terapia neoadyuvante
- Diatermia
Otros números de identificación del estudio
- UFPC-26-01
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Data will be sharing under request due to ethic limitations
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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