Combination Chemotherapy + Radiation for Rectal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Jonsson Comprehensive Cancer Center
Disqualifiers: Active malignancy, Metastatic disease, Pregnancy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This phase I trial investigates how well short-course radiation therapy followed by combination chemotherapy works in treating patients with stage II-III rectal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as leucovorin, fluorouracil, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving short-course radiation therapy and combination chemotherapy may reduce the need for surgery and therefore improve quality of life.
Will I have to stop taking my current medications?
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 evidence supports the effectiveness of the drug combination of Capecitabine, Xeloda, Fluorouracil, and Oxaliplatin with radiation for rectal cancer?
Research shows that using Capecitabine (Xeloda) or Fluorouracil (5-FU) with radiation can effectively reduce tumor size and improve outcomes in rectal cancer. Adding Oxaliplatin to this combination may enhance these effects, although more studies are needed to confirm this.
12345Is the combination of chemotherapy and radiation for rectal cancer safe for humans?
The combination of chemotherapy drugs like capecitabine (Xeloda) and 5-fluorouracil (5-FU) with radiation therapy has been shown to have a favorable safety profile in treating rectal cancer. Common side effects include hand-foot syndrome and mild, reversible leukopenia (low white blood cell count), but severe diarrhea is not common. These treatments have been well-tolerated in clinical trials, making them a generally safe option for patients.
15678What makes this treatment for rectal cancer unique?
This treatment combines chemotherapy drugs like capecitabine and oxaliplatin with advanced radiation therapy (Intensity-Modulated Radiation Therapy) to potentially improve outcomes by reducing tumor size before surgery. The combination aims to enhance the effectiveness of radiation and chemotherapy, offering a promising alternative to traditional treatments.
123910Eligibility Criteria
This trial is for adults with stage II-III rectal adenocarcinoma confirmed by lab tests, without metastatic disease. They should be in good enough health to perform daily activities (KPS >= 70 or ECOG 0-2) and have normal blood counts and liver function tests. Pregnant or breastfeeding individuals, those with other active cancers, prior radiation in the same area, or conditions preventing MRI are excluded.Inclusion Criteria
Hemoglobin (Hgb) > 8.0 gm/dL
Platelets (PLT) > 150,000/mm^3
Total bilirubin <= 1.5 x upper limit of normal
+8 more
Exclusion Criteria
I am currently being treated for another type of cancer.
Pregnant and/or breastfeeding
I've had radiation in the same area where my current cancer is located.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Radiation
Participants undergo short-course radiation therapy in the form of intensity-modulated radiation therapy (IMRT) over 5 fractions daily for 5 consecutive days
1 week
5 visits (in-person)
Chemotherapy
Participants receive either mFOLFOX6 or CapeOX chemotherapy regimens. mFOLFOX6 is administered every 2 weeks for up to 8 cycles, and CapeOX is administered every 3 weeks for up to 6 cycles
16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment. NOM patients are followed up every 3 months for 2 years, then every 6 months for 3 years. TME patients are followed up every 3-6 months for 2 years, then every 6 months for 3 years
5 years
Participant Groups
The study is testing if a short course of high-energy x-ray radiation followed by chemotherapy drugs like leucovorin, fluorouracil, oxaliplatin, and capecitabine can shrink tumors in rectal cancer patients without immediate surgery. The goal is to see if this approach improves quality of life by delaying or avoiding surgery.
1Treatment groups
Experimental Treatment
Group I: Treatment (IMRT, mFOLFOX6, CapeOX, TME)Experimental Treatment8 Interventions
Patients undergo SCRT in the form of IMRT over 5 fractions daily for 5 consecutive days. Beginning 11-18 days after the last day of radiation therapy, patients receive either oxaliplatin IV and leucovorin IV on day 1 and fluorouracil IV on days 1-3 (mFOLFOX6) or oxaliplatin IV on day 1 and capecitabine PO BID on days 1-14 (CapeOX). Treatment with mFOLFOX6 repeats every 2 weeks for up to 8 cycles, and treatment with CapeOX repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. At 8-12 weeks after completion of all therapy, patients with residual tumor undergo TME. Patients with cCR undergo NOM.
Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:
πͺπΊ Approved in European Union as Xeloda for:
- Colorectal cancer
- Breast cancer
πΊπΈ Approved in United States as Xeloda for:
- Colorectal cancer
- Breast cancer
π¨π¦ Approved in Canada as Xeloda for:
- Colorectal cancer
- Breast cancer
π―π΅ Approved in Japan as Xeloda for:
- Colorectal cancer
- Breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
The Joseph Drown FoundationCollaborator
Natera, Inc.Industry Sponsor
References
Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.
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.
Integrated treatment with doxifluridine and radiotherapy in recurrent or primary unresectable rectal cancer. A feasibility study. [2022]When combined with radiotherapy, fluoropyrimidines have been shown to have synergistic effects on various tumor types. Doxifluridine (5-dFUR) is a 5-fluorouracil (5-FU) prodrug that is transformed into 5-FU in neoplastic tissue, which suggests that it may improve the activity of radiotherapy. The aims of this study were to evaluate the feasibility and efficacy of the combination of radiotherapy and oral 5-dFUR plus l-leucovorin in terms of pathologically complete remissions in locally advanced rectal cancer.
Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. [2022]The aim of this study was to determine the efficacy of capecitabine (Xeloda), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC).
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.
Oral capecitabine: bridging the Atlantic divide in colon cancer treatment. [2018]5-Fluorouracil (5-FU) plus leucovorin (LV) has been the mainstay of treatment for colorectal cancer (CRC), with infused schedules more widely adopted in Europe and bolus schedules preferred in North America. However, the effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV on both sides of the Atlantic. Capecitabine generates 5-FU preferentially in tumor and is a well-established, first-line treatment for metastatic CRC. In this setting, capecitabine achieves a superior response rate, at least equivalent time to disease progression (TTP) and overall survival, and favorable safety compared with bolus 5-FU/LV. The benefits of capecitabine have been transfered into the adjuvant setting. Recent data from a large, international, randomized trial (Xeloda Adjuvant Chemotherapy Trial [X-ACT]) confirm that capecitabine (Xeloda, Roche Laboratories, Nutley, NJ) achieves favorable safety versus 5-FU/LV (Mayo Clinic regimen) and is at least as effective as IV 5-FU/LV in the adjuvant treatment of patients with resected stage III colon cancer. Capecitabine is also an effective and well-tolerated combination partner for oxaliplatin (XELOX) and irinotecan (XELIRI), achieving high efficacy with a good safety profile. An extensive phase III clinical trial program is further establishing the potential of the simplified capecitabine combinations to improve outcomes and unify treatment practices in the metastatic and adjuvant settings. New combinations with novel agents such as capecitabine/oxaliplatin plus erlotinib or bevacizumab are currently under investigation. Capecitabine has also shown promising activity and good tolerability in combination with radiotherapy in rectal cancer.
Radiotherapy and oral capecitabine in the preoperative treatment of patients with rectal cancer: rationale, preliminary results and perspectives. [2022]Preoperative radiotherapy alone or combined with chemotherapy increases the chances of tumor down-staging and down-sizing and facilitates sphincter-sparing surgical procedures, thereby improving survival and quality of life. Though several innovative agents are being investigated in combination with radiotherapy, 5-fluorouracil in continuous infusion remains the common schedule used in the preoperative chemoradiation setting. However, the protracted venous infusion of 5-fluorouracil requires specialized pumps and long-term venous access, which makes patients susceptible to infections or thrombosis. To overcome the 5-fluorouracil infusion-related problems, oral 5-fluorouracil precursors and inhibitors of 5-fluorouracil degradation have been developed and explored. These include oral fluoropyrimidines such as tegafur (ftorafur), uracil plus tegafur (UFT), S-1, eniluracil and the oral carbamate capecitabine. Phase I trials have demonstrated the feasibility of the capecitabine-radiotherapy combination with respect to the bolus or infusion 5-fluorouracil-radiation approach and have defined the optimal dose of capecitabine during radiotherapy (825 mg/m2/day through a bid administration). Severe hand-foot syndrome occurred in 7-15% of patients, representing the most commonly observed toxicity. It is noteworthy that severe diarrhea with capecitabine during radiotherapy was not common. Leukopenia frequently occurred but was mild and reversible. Phase II trials, although limited in number, have evidenced a high probability of pathological complete response (up to 31%) with capecitabine and radiation, with an increased probability of sphincter-sparing surgical procedures. Although it is too early to assess whether oral capecitabine will be able to replace iv 5-fluorouracil in combination with preoperative radiotherapy, the NSABP will address this question in a large randomized trial. Finally, phase I-II trials evaluating escalating doses of capecitabine associated with oxaliplatin or irinotecan with radiotherapy are being carried out to assess the maximum-dose tolerance and efficacy in the preoperative setting. It is likely that these new chemoradiation associations might increase rectal cancer clearance, hopefully without increasing toxicity.
Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. [2019]5-Fluorouracil-based chemotherapy with concurrent radiotherapy (RT) is the standard adjuvant treatment in rectal cancer. A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicities of capecitabine combined with standard RT as adjuvant treatment in patients with rectal cancer.
Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. [2022]To evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer.
Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer. [2013]To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer.