- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT03010722
Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Regorafenib Monotherapy (PROSPECT-R)
A Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Regorafenib Monotherapy in RAS Mutant Metastatic Colorectal Cancer
Přehled studie
Detailní popis
Typ studie
Zápis (Aktuální)
Kontakty a umístění
Studijní místa
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Surrey
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Carshalton, Surrey, Spojené království, SM2 5PT
- The Royal Marsden NHS Foundation Trust London and Surrey
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
Popis
Inclusion Criteria:
- Patients with RAS mutant (MT) metastatic colorectal cancer (mCRC) who have been at least once treated with available therapies including fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan and an anti-angiogenic agent, except for patients who have not been treated with oxaliplatin due to previous documented peripheral neuropathy in an adjuvant setting or in those patients where disease has progressed within a short time from receiving adjuvant treatment (<12 months).
- Eligible to receive regorafenib within the context of PROSPECT-R trial at the Royal Marsden Hospital
Exclusion criteria:
A patient who meets any of the exclusion criteria will NOT be eligible for randomization.
A patient must NOT
- have had prior treatment with regorafenib or any other VEGF-targeting kinase inhibitor
- have had previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Noninvasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
- Patients that are participating in another clinical trial involving an investigational medicinal product, unless it is more than 14 days after they have ceased the investigational medicinal product
- Patients that are participating in another research study involving tumour tissue biopsies planned to take place during the time that the patient is participating in this study
- Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
- If female and of childbearing potential, be engaged in breast feeding
- Be unable to swallow oral tablets (crushing of study treatment tablets is not allowed)
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Ongoing infection > Grade 2 NCI Common Toxicity Criterial for Adverse Effects (CTCAE).
- Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management
- Have congestive heart failure classified as New York Heart Association Class 2 or higher
- Have had unstable angina (angina symptoms at rest) or new-onset angina < 3 months prior to screening
- Have had a myocardial infarction < 6 months prior to initiation of study treatment
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
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Regorafenib
160 mg orally (po) od for 3 weeks of every 4-week cycle All patients will be required to have pre-treatment dynamic contrast enhance computed tomography (DECT) scan pre-treatment and at 8 weeks. Suitable patients will also be required to have dynamic contrast enhanced magnetic resonance imaging (DEC-MRI) and diffusion weighted (DW)-MRI, pre-treatment and at 2 weeks. All patients will also be required to have an Ultrasound (USS) or CT-guided biopsy of suitable metastatic lesion. |
Patients meeting all of the inclusion criteria and none of the exclusion criteria will receive regorafenib 160 mg orally (po) od for 3 weeks of every 4-week cycle.
Each cycle will comprise 3 weeks of treatment followed by 1 week without treatment, hereafter described as "3 weeks on/1 week off".
Each 160-mg dose will include four regorafenib 40-mg tablets.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
disease control rate (DCR), measured in months
Časové okno: 12 months
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DCR will be defined as complete response (CR)/partial response (PR)/ stable disease (SD) using RECIST v1.1.
Chi2 or Fisher's exact tests will be employed to explore whether there is an association between low or high mutations and DCR.
Logistic regression will be employed to produce odds ratios (ORs) and 95% confidence intervals (CIs).
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12 months
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
progression free survival (PFS), measured in months
Časové okno: 12 months
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PFS will be measured from start of treatment to date of progression or death from any cause.Logistic regression will be employed to produce odds ratios (ORs) and 95% confidence intervals (CIs).
The PFS will be estimated using the Kaplan-Meier method and survival curves will be generated for each group.
The log-rank test will be used to compare the survival curves and a Cox proportional hazards model will be fitted to obtain hazard ratios (HRs) and 95% CIs.
The proportional hazards assumption will be tested with the use of Schoenfeld residuals
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12 months
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overall survival (OS), measured in months
Časové okno: 12 months
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OS will be defined as time from start of treatment to death of any cause.
Logistic regression will be employed to produce odds ratios (ORs) and 95% confidence intervals (CIs).
The OS will be estimated using the Kaplan-Meier method and survival curves will be generated for each group.
The log-rank test will be used to compare the survival curves and a Cox proportional hazards model will be fitted to obtain hazard ratios (HRs) and 95% CIs.
The proportional hazards assumption will be tested with the use of Schoenfeld residuals
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12 months
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Median values of volume transfer constant (Ktrans) and enhancing fraction (EF) and their product KEF (product of summarised median values of Ktrans x EF/100) will be compared at baseline and on day 15
Časové okno: 15 days
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Dynamic contrast enhance magnetic resonance imaging (DCE-MRI) will be performed pre-treatment and at day 15.
KEF changes of more than 70% between the two time points will be considered significant and patients will be thus stratified in two groups, i.e.
A) drop in KEF of >70% and B) less than 70% drop in KEF.
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15 days
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Spolupracovníci a vyšetřovatelé
Spolupracovníci
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 4164
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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