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SNCTP000002073 | NCT02910843 | BASEC2016-01778

SAKK 41/16-RECAP
Präoperative Behandlung mit Regorafenib und Capecitabine zusammen mit Radiotherapie in lokal fortgeschrittenem Enddarmkrebs. Eine multizentrische Phase Ib Studie.

Base di dati: BASEC (Importata da 24.11.2020), WHO (Importata da 22.11.2020)
Cambiato: 17.06.2020
Categoria di malattie: Cancro del colon-retto

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Ziel dieser Studie ist es, die Sicherheit, Verträglichkeit und Wirkung einer zusätzlichen Therapie von Regorafenib zur präoperativen Standardtherapie mit Bestrahlung und Chemotherapie mit Capecitabine/Xeloda® zu testen. Wir wollen untersuchen ob die zusätzliche Einnahme von Regorafenib zur Standard-Radio-Chemotherapie mit Capecitabine/Xeloda® verträglich und wirksam ist. Es handelt sich bei Regorafenib um einen „Multi-Tyrosin-Kinase Inhibitor“. Das bedeutet, der Wirkstoff stört in der Krebszelle den Stoffwechsel an verschiedenen Schlüsselstellen und hemmt so die Weiterverbreitung des Tumors. Regorafenib hat auch eine hemmende Wirkung auf die Neubildung von Blutgefässen (Arterien und Venen), welche für das Tumorwachstum wichtig sind.
Regorafenib wurde bis anhin noch nie in Kombination mit der Radiotherapie oder mit Capecitabine/Xeloda® verabreicht.

Malattie studiate (Fonte di dati: BASEC)

lokal fortgeschrittener Enddarmkrebs

Health conditions (Fonte di dati: WHO)

Rectal Cancer

Malattia rara (Fonte di dati: BASEC)

No

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: BASEC)

Die Studien-Behandlung dauert insgesamt über 5 ½ Wochen. Anschliessend erfolgt die operative Entfernung des Tumors. Danach folgt während 3 Jahren eine Nachsorge-Phase.
Zusammengefasst besteht die Studie aus den folgenden aufeinanderfolgenden Phasen:
• Eine Voruntersuchungs-Phase, in der Untersuchungen zur genauen Überprüfung Ihres Gesundheitszustandes und Ihrer medizinischen Eignung für diese Studie stattfinden
• Eine Behandlungs-Phase
• Eine Nachsorge-Phase, um zu ermitteln, wie sich die Behandlung bei Ihnen ausgewirkt hat bzw. langfristig auswirkt.

Behandlungs-Phase:

Interventions (Fonte di dati: WHO)

Drug: Regorafenib;Drug: Capecitabine;Radiation: Radiotherapy;Procedure: Surgery

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

- Stadium 2 und 3 gemäss AJCC 2012, mrT3/4 N0, mrTx N1-2 cM0 (beurteilt mit einem obligatorischen CT Scan Brust/Bauch, MRI Becken). TNM Klassifizierung, MRI Qualitätskontrolle empfohlen.
-Kein DPD-Mangel (Dihydro-Pyrimidin-Dehydrogenase DPD Test obligatorisch).
-Ausreichende Organ-Funktion

Criteri di esclusione (Fonte di dati: BASEC)

- Nachweis in der Krankengeschichte einer hämatologischen oder primären soliden Tumorerkrankung, wenn nicht in Remission/Rückbildung während mindestens 3 Jahren ab Registrierung mit der Ausnahme eines ädequat-behandelten in situ Gebärmutterhalskrebses oder eines lokalisierten weissen Hautkrebses.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


Inclusion Criteria:

- Written informed consent according to Swiss law and ICH/GCP regulations before any
trial specific procedures.

- Histologically confirmed and clinically advanced adenocarcinoma. pStage 2 and 3
according AJCC 2012, mrT3/4 N0, mrTx N1-2 cM0 (assessed by mandatory CT scan
thorax/abdomen, MRI pelvis). TNM classification; recommended MRI quality assurance.

- Tumor is located in the lower and middle rectum (caudal end is defined at maximum of
12 cm from anal verge measured by endoscopy).

- A multi-disciplinary tumor board recommends neoadjuvant radio-chemotherapy and
surgery.

- No DPD deficiency (Dihydro-pyrimidine-dehydrogenase DPD deficiency test mandatory).
Carrier status of a predefined risk allele of the dihydro-pyrimidine-dehydrogenase
gene (DPYD), defined as the presence of at least one of the following mutations:
c.1679T>G, c.1905+1G>A, c.2846A>T, c.1129-5923C>G.

- Age 18 to 75 years.

- WHO performance status 0-1.

- Adequate bone marrow function: neutrophils = 1.5 x 109/L, platelets = 100 x 109/L,
hemoglobin = 100 g/L.

- Adequate hepatic and pancreatic function: bilirubin = 1.5 x ULN, AST/ALT/AP = 2.5 x
ULN, Lipase = 1.5 x the ULN.

- Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the
formula of Cockcroft-Gault).

- INR = 1.5 or PTT = 1.5 x ULN (patients who are being therapeutically anticoagulated
are not allowed to participate in the trial). If anti coagulation is indicated during
trial treatment, low molecular weight heparin must be used.

- Women with child-bearing potential are using effective contraception, are not pregnant
and agree not to become pregnant during trial treatment and during the 8 weeks
thereafter. A negative pregnancy test before inclusion into the trial is required for
all women with child-bearing potential.

- Men agree to use effective contraception during trial treatment and 8 weeks
thereafter.

Exclusion Criteria:

- History of hematologic or primary solid tumor malignancy, unless in remission for at
least 3 years from registration with the exception of adequately treated cervical
carcinoma in situ or localized non-melanoma skin cancer.

- Concurrent or recent (within 30 days of registration) treatment with any other
experimental drug.

- Any prior treatment for rectal cancer.

- Major surgery or significant traumatic injury within 28 days before registration
(colostomy accepted).

- Concomitant strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir,
telithromycin, voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine,
phenobarbital, phenytoin, rifampin, St. John's Wort) within 28 days or 5 drug
half-lives (if drug half-life in patients is known), whichever is shorter, before
start of trial treatment (see http://medicine.iupui.edu/).

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA II-IV),
unstable angina pectoris, history of myocardial infarction within the last six months,
serious arrhythmias requiring medication (with exception of atrial fibrillation or
paroxysmal supraventricular tachycardia), significant QT-prolongation (QTc interval
>460 msec), uncontrolled hypertension (sustained systolic blood pressure > 150 mm Hg
and/or diastolic > 100 mm Hg despite antihypertensive therapy).

- Patients with evidence or history of any bleeding diathesis, irrespective of severity.

- Any hemorrhage or bleeding event = Grade 3, NCI-CTCAE v4.03 within 4 weeks prior to
the start of trial medication.

- Significant proteinuria: Positive dipstick 2+ and greater if proteinuria = 3.5g/24 h
measured by urine protein-creatinine ratio is confirmed (= Grade 3, NCI-CTCAE v4.0).

- Patients with known hepatopathy as cirrhosis or diseases like Morbus Gilbert
Meulengracht.

- Interstitial lung disease with ongoing signs and symptoms at the time of informed
consent.

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment.

- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
syndrome.

- History of organ allografts.

- Known hypersensitivity to any of the trial drugs, trial drug classes, or excipients in
the formulation.

- Breast-feeding patients.

- Any concomitant drugs contraindicated for use with the trial drugs according to the
Swissmedic approved product information.

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT02910843

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02910843

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

14.09.2016

Inserimento del primo partecipante

22.02.2017

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer. A Multicenter Phase Ib Trial (RECAP)

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional

Disegno della sperimentazione (Fonte di dati: WHO)

Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Fase (Fonte di dati: WHO)

Phase 1

Punti finali primari (Fonte di dati: WHO)

Dose limiting toxicity (DLTs);Pathological near complete or complete tumor response (npCR or pCR)

Punti finali secondari (Fonte di dati: WHO)

Quality of the mesorectal excision including details of the circumferential resection margin (CRM)/surface;Sphincter preservation;Pathological response;Circumferential resection margin (CRM) status;Downstaging of primary tumor and/or lymph nodes (comparison between mrT/N and ypT/N);Postoperative complications

Contatto per informazioni (Fonte di dati: WHO)

Please refer to primary and secondary sponsors

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Basilea, Berna, Chur, Luzern, San Gallo, Zurigo

Paesi di esecuzione (Fonte di dati: WHO)

Switzerland

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

Daniela Bärtschi
+41 31 389 91 91
trials@sakk.ch

Contatto per informazioni generali (Fonte di dati: WHO)

Sara Bastian, MD;Daniela Bärtschi
Kantonsspital Graubünden, Chur
+41 31 389 91 91
trials@sakk.ch

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Sara Bastian, MD;Daniela Bärtschi
Kantonsspital Graubünden, Chur
+41 31 389 91 91
trials@sakk.ch

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Swiss Group for Clinical Cancer Research

Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)

Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)

Kantonale Ethikkommission Zürich

Data di autorizzazione da parte della commissione d’etica

24.02.2017

Altri numeri di identificazione delle sperimentazioni

Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID) (Fonte di dati: BASEC)

2016-01778

Secondary ID (Fonte di dati: WHO)

SAKK 41/16 - RECAP