Chemoradiation + Radiation Boost for Rectal Cancer
(Morpheus Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Sir Mortimer B. Davis - Jewish General Hospital
Must be taking: 5-FU, Xeloda
Disqualifiers: Previous pelvic radiation, Metastasis, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
A randomized study of 131 patients. Patients with a clinical T2-3 N0 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions).
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug Xeloda (capecitabine) for rectal cancer?
Is the treatment of chemoradiation with 5-FU or capecitabine generally safe for humans?
What makes the Chemoradiation + Radiation Boost treatment for rectal cancer unique?
Eligibility Criteria
This trial is for adults over 18 with early-stage rectal cancer that hasn't spread, can be seen via colonoscopy, and is within 10 cm of the anal verge. The tumor must be less than 5 cm, occupy less than half the circumference of the rectum, and not have penetrated deeply into surrounding fat. Participants need to use effective birth control if applicable.Inclusion Criteria
My cancer has not spread to other parts of my body.
Adequate birth control measures in women of childbearing potential
Written informed consent
See 10 more
Exclusion Criteria
My cancer has spread to distant parts of my body.
My cancer has spread to the anal canal.
My cancer is at a stage where it has grown very large or spread to nearby tissues.
See 2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) followed by either an external beam boost of 9 Gy or a brachytherapy boost of 30 Gy in 3 fractions
6-8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments for local recurrence and overall survival
5 years
Treatment Details
Interventions
- 5-FU (Chemotherapy)
- Chemoradiation + EBRT Boost (Radiation)
- Chemoradiation + HDRBT Boost (Radiation)
- HDRBT Boost (Brachytherapy)
- Xeloda (Chemotherapy)
Trial OverviewThe study compares two treatments after standard chemoradiation for rectal cancer: one group receives an external beam radiation boost (EBRT), while another gets a high-dose-rate brachytherapy boost (HDRBT). Patients are randomly assigned to either treatment arm.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Chemoradiation + HDRBT BoostExperimental Treatment2 Interventions
standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions; Complete responders and Non-complete responders
Group II: Chemoradiation + EBRT BoostExperimental Treatment2 Interventions
standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy in 5; Complete responders and Non-complete responders
5-FU is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇪🇺 Approved in European Union as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
- Skin cancer
🇨🇦 Approved in Canada as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇯🇵 Approved in Japan as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Le Centre Hospitalier de l'Université de MontrealMontréal, Canada
Centre hospitalier universitaire de QuébecQuébec City, Canada
Jewish General HospitalMontreal, Canada
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Who Is Running the Clinical Trial?
Sir Mortimer B. Davis - Jewish General HospitalLead Sponsor
References
Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer.
Fluoropyrimidines: a critical evaluation. [2017]After nearly four decades of clinical experience with the fluoropyrimidines, 5-fluorouracil (5-FU) remains an integral part of chemotherapy for colorectal cancer. A range of 5-FU treatment regimens with or without biochemical modulation are currently used and toxicity appears to be schedule dependent. The use of oral 5-FU was abandoned because of erratic absorption caused by varying levels of dihydropyrimidine dehydrogenase (DPD) found in the gastrointestinal tract. This effect may be overcome by administering agents that are converted to 5-FU or by inhibiting or inactivating DPD. Xeloda((R)) (capecitabine) was designed as an orally administered, selectively tumoractivated(TM) cytotoxic agent which achieves higher levels of 5-FU in the primary tumor than in plasma or other tissues. The United States Food and Drug Administration (FDA) has approved Xeloda for use in patients with metastatic breast cancer resistant to paclitaxel and in whom further anthracycline therapy is contraindicated. Xeloda is also registered in Canada, Switzerland, Thailand and Argentina. In phase II clinical trials in colorectal cancer, Xeloda produced response rates of 21-24% and median time to disease progression of 127-230 days. Other oral agents in development for the treatment of colorectal cancer include tegafur/uracil plus oral leucovorin, S-1 and eniluracil plus oral 5-FU.
Xeloda in colorectal cancer. [2015]Xeloda (capecitabine) is a rationally designed, oral pro-drug of 5-fluorouracil (5-FU). It is rapidly and almost completely absorbed in the upper gastrointestinal tract. It is then catabolised in a three-enzyme system, the last step being catalysed by thymidine phosphorylase, which is upregulated in many human cancers. Clinical pharmacology studies have confirmed that this preferential activation actually occurs in human colorectal cancer. Phase I and II trials were performed in colorectal cancer to define the optimal dose and schedule of capecitabine. In two large scale phase III studies this agent has been shown to be at least as effective as a standard regimen of bolus 5-FU and leucovorin (Mayo regimen). Response was superior in the capecitabine arms of these studies with equivalence of progression-free and overall survival. In addition the oral regimen was associated with significantly less toxicity. It seems likely that this agent will replace intravenous 5-FU in the therapy of colorectal cancer and possibly in other cancers.
Comparing pathological complete response rate using oral capecitabine versus infusional 5-fluorouracil with preoperative radiotherapy in rectal cancer treatment. [2018]Infusional 5-fluorouracil (5-FU) has been the standard radiation sensitizer in patients undergoing preoperative long-course chemoradiotherapy (CRT) for locally advanced rectal cancer in Australia. Capecitabine (Xeloda) is an oral 5-FU prodrug of comparable pharmacodynamic activity, currently preferred in place of 5-FU infusion, its established counterpart in neoadjuvant CRT for rectal cancer. The few studies quantifying pathological complete response (pCR) of Xeloda versus 5-FU have produced inconsistent results. We reviewed our own data to determine if the rates of pCR of oral capecitabine were non-inferior to intravenous 5-FU in patients undergoing neoadjuvant CRT for rectal cancer.
Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022]To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.
Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. [2022][corrected] Capecitabine (Xeloda) is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumors. The purpose of this study was to demonstrate the preferential activation of capecitabine, after oral administration, in tumor in colorectal cancer patients, by the comparison of 5-FU concentrations in tumor tissues, healthy tissues and plasma.
Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. [2022]Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration.
Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study. [2018]Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses.
Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. [2015]5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation.
Capecitabine and radiation therapy for advanced gastrointestinal malignancies. [2015]Accumulating data indicate a beneficial effect of combining infusional fluorouracil (5-FU) with radiation therapy in gastrointestinal cancers, and phase II/III studies are under way to examine this approach in a variety of tumor types. The oral fluoropyrimidine capecitabine (Xeloda) provides a more convenient approach to radiosensitization. The agent has good single-agent activity in a variety of tumor types. The final step in activation of the drug to 5-FU occurs via activity of thymidine phosphorylase; thymidine phosphorylase activity is markedly upregulated in many tumor tissues compared with healthy tissue (Miwa M, Ura M, Nishida M, et al: Eur J Cancer 34:1274-1281, 1998), allowing greater accumulation of 5-FU in tumor tissue, and there is evidence indicating that radiation therapy results in augmented upregulation of this enzyme. A variety of data suggest benefits of 5-FU as a radiosensitizer in improving outcome of radiation therapy in a number of gastrointestinal cancers, including data indicating improved survival with this chemoradiation therapy approach. Prospective and randomized studies of 5-FU-based chemoradiation are under way in esophageal, gastric, biliary tract, pancreatic, rectal, and anal cancer. Early phase studies are planned to examine the combination of capecitabine, celecoxib (Celebrex), and radiation therapy in esophageal cancer and pancreatic cancer and to compare the effects of capecitabine and capecitabine/oxaliplatin (Eloxatin) with radiation therapy in rectal cancer. A phase III trial comparing capecitabine and infusional 5-FU in chemoradiation therapy in rectal cancer has also been planned. Additional studies should be conducted in gastric, biliary tract, and anal cancer. Capecitabine shows promise in replacing infusional 5-FU as the platform for gastrointestinal chemoradiation therapy.