- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02948348
Study to Nivolumab Following Preoperative Chemoradiotherapy
A Phase 1b/2 Multicenter Study to Investigate the Safety, Efficacy and Proof of Concept (POC) of Nivolumab Monotherapy as a Sequential Therapy Following Preoperative Chemoradiotherapy Patients With Locally Advanced Resectable Rectal Cancer
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
[Phase Ib]
After preoperative CRT, to sequentially administer nivolumab in combination for patients with locally advanced resectable rectal cancer. To evaluate the safety of nivolumab in sequential combination therapy, the onset of dose-limiting toxicity (DLT) and the safety of subsequent surgical therapy, and to decide on a recommended dose (RD) for the phase II part.
[Phase II] PhaseⅡ is composed of 4 cohorts.
Cohort A: First-onset rectal cancer cohort (42 cases) To evaluate the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered following preoperative CRT.
And to search for biomarkers related to therapeutic effects in first-onset cases. Evaluate the safety of surgical treatment.
Cohort B: Rectal cancer with localized recurrence cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in localized recurrence cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort C: Rectal cancer with resectable lung/liver metastasis cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in resectable lung/liver metastasis cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort D: First-onset rectal cancer using ipilimumab-nivolumab combination cohort (25 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (240 mg/body at two-week intervals) and ipilimumab (1 mg/kg at six-week intervals) after preoperative CRT, and search for biomarkers related to therapeutic effects in first-onset cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Type d'étude
Inscription (Anticipé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Hideaki Bando, Dr
- Numéro de téléphone: +81-52-762-6111
- E-mail: voltage_core@east.ncc.go.jp
Sauvegarde des contacts de l'étude
- Nom: Yuichiro Tsukada, Dr
- Numéro de téléphone: 92331 +81-4-7133-1111
- E-mail: voltage_core@east.ncc.go.jp
Lieux d'étude
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Osaka, Japon
- Recrutement
- Osaka National Hospital
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Chiba
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Kashiwa, Chiba, Japon
- Recrutement
- National Cancer Center Hospital East
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Hokkaido
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Sapporo, Hokkaido, Japon
- Recrutement
- Hokkaido University
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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:
(A. Phase Ib and Cohorts A and D only)
A1. Rectal cancer patients who have not undergone treatment for pre-CRT tumors situated 12 cm or less from the lower edge of the AV.
A2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
A3. Pre-CRT clinical stage is clinical T3-4 N-any M0.
A4. Macroscopic radical resection is deemed possible on pre-CRT image diagnosis.
A5. Aged between 20 and 80 years at the time of enrollment.
(B. Cohort B only)
B1. Clinically diagnosed with local recurrence after rectal surgery.
B2. The main site of recurrence is limited to the pelvis by pre-CRT imaging diagnosis.
B3. Macroscopic radical resection is deemed possible on pre-CRT imaging diagnosis.
B4. Aged between 20 and 75 years at the time of enrollment.
(C. Cohort C only)
C1. Rectal cancer patients who have not undergone pretreatment for a pre-CRT tumor which is 12 cm or less from the lower AV.
C2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
C3. The pre-CRT clinical stage is clinical T3-4 N-any M1a (liver) M1a (lungs).
C4. Macroscopic curative resection of the primary rectal lesion is deemed possible on pre-CRT imaging diagnosis.
C5. A metastatic liver tumor or a metastatic lung tumor has been diagnosed as clinically resectable prior to CRT and during clinical trial enrollment.
(D. Common to all cohorts in Phase Ib and Phase II)
D1. Patients who have provided consent through a consent form.
D2. Patients whose Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is 0 or 1 at the time of enrollment.
D3. CRT was administered:
D4. Patients whose CRT adverse events have recovered to Grade 1 or lower based on CTCAE ver.4.0. within 14 days after the end of CRT, and are expected to be able to take nivolumab (patient is still eligible even if adverse events are not restored to Grade 1, provided that the blood cell count satisfies the eligibility criteria specified in point D8).
D5. Patients with no remote metastases as confirmed by imaging at the end of CRT (testing is allowed from 14 days before the end of CRT to the trial enrollment date).
D6. For women who may become pregnant (including patients who are not menstruating due to chemically-induced menopause among other medical reasons), patients who agree to use contraception for at least 23 weeks after the last administration of the investigational drug, starting from the day they provide consent (30 days (ovulation cycle) plus five times the elimination half-life of the investigational drug).
D7. For men, patients who agree to use contraception for at least 31 weeks after the last administration of the investigational drug, starting from the day they provide consent (90 days (spermatogenesis cycle) plus five times the elimination half-life of the investigational drug).
D8. Patients who have the sufficient organ function at the time of enrollment.
Exclusion criteria
Patients diagnosed with active double cancer (synchronous double cancer and double cancer with disease-free period within five years from enrollment).
However, lesions equivalent to intraepithelial or mucosal carcinoma deemed cured by localized treatment are not classified as active double cancer.
- Patients with a history of pelvic irradiation prior to this rectal cancer treatment.
- Patients who have not given consent through the informed consent form.
- Patients deemed by the investigator to be ineligible for the trial.
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: Nivolumab & Ipilimumab(Only Cohort D)
chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
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Capecitabine:Dose of 1650mg/m2,14days, Radiation:45Gy/25 fractions, Nivolumab :240mg on day1 of each cycle, Surgical therapy:The resection (LAR), intersphincteric resection (ISR), or abdominoperineal resection (APR).
Autres noms:
For only Cohort D,1 mg/kg at six-week intervals
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Réponse complète pathologique
Délai: 1 an
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La réponse pathologique complète sera évaluée avec la classification du cancer de l'American Joint Committee on Cancer (AJCC)
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1 an
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Objective response rate
Délai: 1 year
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Evaluation Criteria In Solid Tumors (RECIST)
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1 year
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Recurrence pattern (local or distant)
Délai: 1 year
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1 year
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Disease-free survival (DFS)
Délai: 5years
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Evaluation Criteria In Solid Tumors (RECIST)
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5years
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Overall survival (OS)
Délai: 5years
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Evaluation Criteria In Solid Tumors (RECIST)
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5years
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Incidence of adverse events (AEs)
Délai: 1 year
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Safety will be evaluated with CTCAE v4.0
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1 year
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Rate of completing the protocol therapy
Délai: 1 year
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1 year
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Rate of radical resection
Délai: 1 year
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1 year
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Safety evaluation
Délai: 5years
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Safety will be evaluated with CTCAE v4.0
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5years
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macroscopic evaluation of (rectal cancer) resected specimen
Délai: 1 year
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1 year
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Takayuki Yoshino, Dr, Gastrointestinal Oncology Division National Cancer Center Hospital East
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
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 digestif
- Tumeurs
- Tumeurs par site
- Tumeurs gastro-intestinales
- Tumeurs du système digestif
- Maladies gastro-intestinales
- Maladies intestinales
- Tumeurs intestinales
- Maladies rectales
- Tumeurs colorectales
- Tumeurs rectales
- Mécanismes moléculaires de l'action pharmacologique
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents antinéoplasiques immunologiques
- Inhibiteurs de point de contrôle immunitaire
- Capécitabine
- Nivolumab
- Ipilimumab
Autres numéros d'identification d'étude
- EPOC1504
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Cancer du rectum
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Abramson Cancer Center of the University of PennsylvaniaRetiréPatients cancéreux subissant une greffe de cellules souches (RCT of ACP for Transplant)
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Swansea UniversityComplétéA Bite of ACT '(BOA) Cours de psychoéducation en ligne sur la thérapie d'acceptation et d'engagement | Un contrôle de liste d'attenteRoyaume-Uni
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National Cancer Institute (NCI)ComplétéAdénocarcinome mucineux du rectum | Chevalière Adénocarcinome du Rectum | Cancer rectal de stade IIA | Cancer du rectum de stade IIB | Cancer rectal de stade IIC | Cancer du rectum de stade IIIA | Cancer du rectum de stade IIIB | Cancer du rectum de stade IIIC | Adénocarcinome du rectumÉtats-Unis
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University of Southern CaliforniaNational Cancer Institute (NCI)Actif, ne recrute pasAdénocarcinome mucineux du rectum | Chevalière Adénocarcinome du Rectum | Cancer rectal de stade IIA | Cancer du rectum de stade IIB | Cancer rectal de stade IIC | Cancer du rectum de stade IIIA | Cancer du rectum de stade IIIB | Cancer du rectum de stade IIICÉtats-Unis
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Washington University School of MedicineComplétéCancer rectal | Cancer du rectum | Cancer du rectum | Tumeur, rectum | Cancer du rectum | Tumeurs du rectum | Adénocarcinome du rectumÉtats-Unis
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OHSU Knight Cancer InstituteOregon Health and Science University; Taiho Pharmaceutical Co., Ltd.RecrutementCancer rectal de stade III AJCC v8 | Cancer du rectum de stade IIIA AJCC v8 | Cancer du rectum de stade IIIB AJCC v8 | Cancer du rectum de stade IIIC AJCC v8 | Adénocarcinome rectal | Cancer du rectum de stade IIA AJCC v8 | Cancer du rectum de stade IIB AJCC v8États-Unis
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Fox Chase Cancer CenterNational Cancer Institute (NCI)ComplétéAdénocarcinome mucineux du rectum | Chevalière Adénocarcinome du Rectum | Cancer rectal de stade IIA | Cancer du rectum de stade IIB | Cancer rectal de stade IIC | Cancer du rectum de stade IIIA | Cancer du rectum de stade IIIB | Cancer du rectum de stade IIIC | Cancer rectal récurrentÉtats-Unis
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Virginia Commonwealth UniversityNational Cancer Institute (NCI)ComplétéAdénocarcinome mucineux du rectum | Chevalière Adénocarcinome du Rectum | Cancer rectal de stade IIA | Cancer du rectum de stade IIB | Cancer rectal de stade IIC | Cancer du rectum de stade IIIA | Cancer du rectum de stade IIIB | Cancer du rectum de stade IIIC | Adénocarcinome rectal | Cancer rectal...États-Unis
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Ohio State University Comprehensive Cancer CenterNovartis Pharmaceuticals; National Comprehensive Cancer NetworkComplétéCancer rectal de stade IIA | Cancer du rectum de stade IIB | Cancer rectal de stade IIC | Cancer du rectum de stade IIIA | Cancer du rectum de stade IIIB | Cancer du rectum de stade IIIC | Cancer rectal récurrentÉtats-Unis
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