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.
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Pedro C Lara, MD, PhD
- Numéro de téléphone: +34928012800
- E-mail: plara@ufpcanarias.es
Lieux d'étude
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Las Palmas
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Las Palmas de Gran Canaria, Las Palmas, Espagne, 35010
- Hospital Universitario de Gran Canaria Dr Negrín
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Contact:
- Laura Ferrera-Alayón, MD, Phd
- Numéro de téléphone: +34928450000
- E-mail: lferala@gobiernodecanarias.org
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Malaga
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Málaga, Malaga, Espagne
- Hospital Universitario Quirón Salud
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Contact:
- Jorge Contreras, MD, PhD
- Numéro de téléphone: +34 951 94 00 00
- E-mail: jorgecontrerasmartinez@gmail.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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 |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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overall survival
Délai: one year
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Time from included in the study to death for any cause |
one year
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Progression Free Survival
Délai: 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)
Délai: 6 months
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according to RECIST 1.1. |
6 months
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disease control rate (DCR),
Délai: 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.
Délai: 6 months
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Modifications CEA and CA19.9 values |
6 months
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Conversion rate to surgery.
Délai: 6 months
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Resectabiity after neoadjuvant treatment |
6 months
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R0 resection rate
Délai: 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.
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Pedro C Lara, Md, PhD, Universidad Fernando Pessoa Canarias
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système endocrinien
- Blessures et Blessures
- Tumeurs par site
- Tumeurs
- Tumeurs du système digestif
- Maladies du système digestif
- Tumeurs des glandes endocrines
- Maladies pancréatiques
- Changements de température corporelle
- Troubles liés au stress thermique
- Conditions pathologiques, signes et symptômes
- Signes et symptômes
- Hyperthermie
- Tumeurs pancréatiques
- Thérapeutique
- Hyperthermie, induite
- Thérapie de modalité combinée
- Thérapie néoadjuvante
- Diathermie
Autres numéros d'identification d'étude
- UFPC-26-01
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Data will be sharing under request due to ethic limitations
Informations sur les médicaments et les dispositifs, documents d'étude
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