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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.

Data source: BASEC (Imported from 24.11.2020), WHO (Imported from 22.11.2020)
Changed: 17.06.2020
Disease category: Colon and Rectal Cancer

Brief description of trial (Data source: 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.

Health conditions investigated (Data source: BASEC)

lokal fortgeschrittener Enddarmkrebs

Health conditions (Data source: WHO)

Rectal Cancer

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: 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 (Data source: WHO)

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

Criteria for participation in trial (Data source: 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

Exclusion criteria (Data source: 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 (Data source: 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.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02910843

Further information on the trial from WHO database (ICTRP)

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

Further information on trial

Date trial registered

14.09.2016

Incorporation of the first participant

22.02.2017

Recruitment status

Recruiting

Academic title (Data source: WHO)

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

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

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

Phase (Data source: WHO)

Phase 1

Primary end point (Data source: WHO)

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

Secundary end point (Data source: 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

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Basel, Bern, Chur, Luzern, St. Gallen, Zurich

Countries (Data source: WHO)

Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

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

Contact for general information (Data source: WHO)

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

Contact for scientific information (Data source: WHO)

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

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Swiss Group for Clinical Cancer Research

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

24.02.2017

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2016-01778

Secondary ID (Data source: WHO)

SAKK 41/16 - RECAP