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- Klinische proef NCT01376453
Pre-operative 5-Fluorouracil (5-FU) and Sorafenib With External Radiation in Locally Advanced Rectal Cancer
Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
The main purpose of this study is to find the maximum tolerable dose of sorafenib when administered along with another drug called 5-Fluorouracil (5-FU) and to find out more about whether these drugs, along with radiation, can help people with rectal cancer when given before surgery. 5-FU and radiation are both approved by the US Food and Drug Administration (FDA) for use in people with rectal cancer.
The investigators will utilize a standard 3 + 3 phase I study design. In the phase I part of the study, the investigators will attempt dose escalation of sorafenib in combination with standard infusional 5-FU and external beam at standard doses. Clinical staging should be done by endorectal ultrasound (ERUS) and/or pelvic magnetic resonance imaging (MRI) for T and N stage; chest and abdomen computed tomography (CT) for staging of metastatic disease; undergo sigmoidoscopy and/or colonoscopy done by crude odds ratios (CORS); biopsy is taken for diagnosis and extra is sent for tissue bank. At the maximum tolerated dose (MTD) of sorafenib we will expand the cohort to 6 more patients to further evaluate toxicity profile and efficacy.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Participants' study regimen will include 5 ½ weeks of radiation. Radiation sessions will be daily, Monday through Friday, except for holidays. 5-FU will be delivered at a dose of 225 mg/m² daily through a catheter in a large vein continuously until the last day of radiation. In addition, sorafenib will be taken by mouth twice daily every day until the last day of radiation. The dose of sorafenib participants may receive will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily. Following completion of this phase of the study, participants will receive no study drug or radiation for one month. At 4 to 5 weeks after stopping study drug and radiation, participants will have another CT scan or MRI to assess their cancer. About 6 to 8 weeks after the end of radiation, participants will undergo surgery and every effort will be made to remove the tumor. The surgery will occur just as it would if participants were not in the study, except that a portion of their tumor obtained during surgery will be used for research biomarker testing (as described in the consent form).
Approximately 6 -10 weeks after participants' surgery, when they have adequately healed, they may receive additional chemotherapy at their study doctor's discretion.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Florida
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Tampa, Florida, Verenigde Staten, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of the rectum that begins within 12 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of distant metastasis
- Locally advanced rectal cancer determined by any of the following features: Fixed or immobile tumor on physical exam and/or; T3 disease with invasion through the muscularis propria as defined by transrectal ultrasound, CT or MRI; T4 disease with invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder and/or prostate as determined appropriate imaging modalities such as ultrasound, CT or MRI; Any T with + N on CT scan/MRI or transrectal ultrasound
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin > 9.0 g/dl, Absolute neutrophil count (ANC) > 1,500/mm^3, Platelet count > 100,000/mm^3, Total bilirubin < 1.5 times upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the ULN ( < 5 x ULN for patients with liver involvement), Creatinine < 1.5 times ULN
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
- Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until international normalized ratio (INR) is stable.
Exclusion Criteria:
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Pelvic irradiation therapy.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, deep vein thrombosis (DVT) within the past 6 months.
- No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer or Treated non-pelvic cancer from which the patient has been continuously disease free more than five years.
- Needing medical attention for serious bleeding in past 4 weeks.
- Previous chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor (TKI) will be allowed as long as it is more than 5 years.
- Evidence or history of bleeding diathesis
- Use of St. John's Wort or rifampin
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Sorafenib Dose Escalation
Pre-operative Continuous 5-FU, and Sorafenib with External Radiation Therapy.
Dose level -1 will only be evaluated if dose level 1 exceeds MTD.
The sorafenib and infusional 5-FU will only be given Day 1-5(Monday-Friday) with radiation only.
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In addition to radiation and 5-FU, sorafenib will be taken by mouth daily every day until the last day of radiation.
The dose of sorafenib will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily
Andere namen:
5-FU will be delivered at a dose of 225 mg/m^2 daily through a catheter in a large vein continuously until the last day of radiation.
Andere namen:
Radiation sessions will be daily, Monday through Friday, except for holidays.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Maximum Tolerated Dose (MTD)
Tijdsspanne: Start of treatment through end of follow up - average of 21 weeks
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To determine maximally tolerated dose of sorafenib when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinoma
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Start of treatment through end of follow up - average of 21 weeks
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Number of Participants With Pathologic Response
Tijdsspanne: Start of treatment through end of follow up - average of 21 weeks
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To determine the pathologic response rate after pre-operative therapy and surgery
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Start of treatment through end of follow up - average of 21 weeks
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Number of Participants With Serious Adverse Events (SAEs)
Tijdsspanne: Start of treatment through end of follow up - average of 21 weeks
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To further define safety profile of the combination.
During the 5 1/2 weeks of radiation, participants will be seen in the study clinic and will have blood tests weekly.
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Start of treatment through end of follow up - average of 21 weeks
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Medewerkers en onderzoekers
Medewerkers
Publicaties en nuttige links
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- Neoplasmata
- Neoplasmata per site
- Gastro-intestinale neoplasmata
- Neoplasmata van het spijsverteringsstelsel
- Gastro-intestinale aandoeningen
- Darmziekten
- Intestinale neoplasmata
- Rectale ziekten
- Colorectale neoplasmata
- Rectale neoplasmata
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antimetabolieten, antineoplastische
- Antimetabolieten
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Proteïnekinaseremmers
- Fluoruracil
- Sorafenib
Andere studie-ID-nummers
- MCC-16475
- IST 000575 (Andere identificatie: Bayer Corporation)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Rectale kanker
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)VoltooidAdenocarcinoom van de dunne darm | Stadium III Adenocarcinoom van de dunne darm AJCC v8 | Stadium IIIA Adenocarcinoom van de dunne darm AJCC v8 | Stadium IIIB dunne darm adenocarcinoom AJCC v8 | Stadium IV Adenocarcinoom van de dunne darm AJCC v8 | Ampulla van Vater Adenocarcinoom | Stadium III... en andere voorwaardenVerenigde Staten
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University of UtahNational Cancer Institute (NCI)WervingVermoeidheid | Sedentaire levensstijl | Gemetastaseerd prostaatcarcinoom | Stadium IV prostaatkanker AJCC (American Joint Committee on Cancer) v8 | Stadium IVA prostaatkanker AJCC (American Joint Committee on Cancer) v8 | Stadium IVB prostaatkanker AJCC (American Joint Committee on Cancer) v8Verenigde Staten
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Georgetown UniversityNational Cancer Institute (NCI); American Cancer Society, Inc.; Susan G. Komen...VoltooidBestudeer Chinese vrouwen die zich niet hebben gehouden aan de richtlijnen voor screening op mammografie van de American Cancer SocietyVerenigde Staten
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Novartis PharmaceuticalsVoltooidGeavanceerde Triple Negative Breast Cancer (TNBC) met hoge TAM'sFrankrijk, Italië, Oostenrijk, Taiwan, Verenigde Staten, Spanje, Australië, Korea, republiek van, België, Duitsland, Hongkong, Kalkoen
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BioNTech SESeventh Framework ProgrammeVoltooidBorstkanker (Triple Negative Breast Cancer (TNBC))Zweden, Duitsland
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Rashmi Verma, MDNational Cancer Institute (NCI)WervingCastratieresistent prostaatcarcinoom | Gemetastaseerd prostaatadenocarcinoom | Stadium IVB Prostaatkanker American Joint Committee on Cancer (AJCC) v8Verenigde Staten
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Jonsson Comprehensive Cancer CenterNog niet aan het wervenProstaatcarcinoom | Stadium IVB Prostaatkanker American Joint Committee on Cancer (AJCC) v8Verenigde Staten
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University of Southern CaliforniaNational Cancer Institute (NCI)WervingLokaal gevorderd pancreasadenocarcinoom | Inoperabel pancreasadenocarcinoom | Fase III Pancreaskanker American Joint Committee on Cancer v8Verenigde Staten
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)Nog niet aan het wervenAnatomische fase II borstkanker AJCC v8 | Anatomische fase III borstkanker AJCC v8 | Borstcarcinoom in een vroeg stadium | Anatomische fase I Borstkanker American Joint Committee on Cancer (AJCC) v8Verenigde Staten
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Jonsson Comprehensive Cancer CenterIngetrokkenProstaat Adenocarcinoom | Prostaatkanker stadium II AJCC v8 | Stadium IIC prostaatkanker AJCC v8 | Stadium IIA prostaatkanker AJCC v8 | Stadium IIB prostaatkanker AJCC v8 | Fase I Prostaatkanker American Joint Committee on Cancer (AJCC) v8Verenigde Staten
Klinische onderzoeken op Sorafenib
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Ohio State University Comprehensive Cancer CenterBayerBeëindigd
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Technical University of MunichVoltooid
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Ottawa Hospital Research InstituteBayerVoltooidGemetastaseerde colorectale kankerCanada
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BayerAmgenVoltooidCarcinoomVerenigde Staten
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British Columbia Cancer AgencyIngetrokkenLokaal geavanceerde plaveiselcelcarcinomen van het hoofd en de nek (SCCHN)Canada
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Yiviva Inc.WervingGeavanceerd hepatocellulair carcinoomVerenigde Staten, Taiwan, China, Hongkong
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Cancer Institute and Hospital, Chinese Academy...VoltooidHepatocellulair carcinoom, radiotherapie, sorafenibChina
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New Mexico Cancer Care AllianceBeëindigdGemetastaseerd niercelcarcinoomVerenigde Staten
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BayerVoltooidHepatocellulair carcinoomTaiwan
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National Cancer Institute (NCI)Actief, niet wervendGastro-intestinale stromale tumorVerenigde Staten