Chemoradiation for Rectal Cancer

(SMART TNT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Benjamin Spieler, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Miami

Must not be taking: Anti-anxiety agents

Disqualifiers: Metastatic disease, Synchronous cancer, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to find out how safe and effective is treating patients with locally advanced rectal cancer (LARC) with chemotherapy first and then follow with radiation therapy to a higher dose than what is usually delivered and see if patients could have complete response and be spared from surgery.

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 data supports the effectiveness of the treatment for rectal cancer?

Research shows that using 5-fluorouracil (5-FU) with radiation therapy before surgery can reduce the chance of cancer coming back and improve survival rates for rectal cancer patients. Capecitabine, an oral form of 5-FU, has similar effectiveness when combined with radiation. Adding oxaliplatin to these treatments has shown promising results in improving responses in early trials. ^{1 2 3 4 5}

Is chemoradiation for rectal cancer generally safe for humans?

Chemoradiation for rectal cancer, using drugs like 5-fluorouracil (5-FU) and capecitabine (Xeloda), is generally considered safe, but it can cause side effects like diarrhea and mouth sores. These side effects can be severe in some cases, so it's important to monitor and manage them during treatment. ^{1 3 6 7 8}

What makes the chemoradiation treatment for rectal cancer unique?

This treatment combines 5-fluorouracil (5-FU), capecitabine, leucovorin, and oxaliplatin, which together enhance the effectiveness of radiation therapy by improving tumor response and potentially reducing recurrence. Capecitabine, an oral drug, offers a convenient alternative to intravenous 5-FU, and the addition of oxaliplatin may lead to better outcomes, although further studies are needed to confirm its routine use. ^{1 3 4 9 10}

Research Team

Benjamin Spieler, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults with newly diagnosed rectal cancer that hasn't spread beyond the pelvis. Participants must have a certain level of physical fitness (ECOG 0-2), acceptable liver function, and no severe heart conditions or immune deficiencies. Pregnant women and those with metal implants incompatible with MRI are excluded.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My tumor is within 18 cm of the anal verge.

Serum liver function tests values within the range of 1.5 x Upper Limit of Normal (within 6 weeks of enrollment)

Exclusion Criteria

Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity

I have had radiation therapy in the pelvic area before.

I do not have severe infections needing IV antibiotics or active TB.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy with either FOLFOX, mFOLFIRINOX, or CAPOX

12-16 weeks

Chemo-radiation Therapy (Plan I)

Participants receive MRI-guided pelvic IMRT and concurrent chemotherapy

5 weeks

Radiation Therapy Boost (Plan II)

Participants not achieving complete Clinical Response receive an accelerated radiation therapy boost

1 week

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

Up to 30 months

Treatment Details

Interventions

• 5-fluorouracil (Anti-metabolites)
• Accelerated Radiation Therapy (Radiation)
• Capecitabine (Anti-metabolites)
• Intensity-modulated radiation therapy (Radiation)
• Leucovorin (Alkylating agents)
• Oxaliplatin (Alkylating agents)

Trial Overview The study tests if starting with chemotherapy followed by higher-than-usual doses of radiation can help patients avoid surgery while effectively treating locally advanced rectal cancer. The chemo drugs used include 5-fluorouracil, Leucovorin, Oxaliplatin, and Capecitabine.

Participant Groups

Group I: SMART TNT Plan II Experimental Treatment 1 Intervention

Plan II boost RT (1 week): For participants not achieving cCR after chemo-radiation. Participants will receive MRI-guided accelerated radiation therapy (ART) boost to the primary tumor. Participants achieving a cCR will continue to follow-up. Participants still showing residual tumor will undergo standard of care treatment including surgery and adjuvant chemotherapy per institutional guidelines during follow-up.

Group II: SMART TNT Plan I Experimental Treatment 6 Interventions

Participants will initiate therapy with neoadjuvant chemotherapy of either six (6) 14-day cycles of 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX), six (6) 14-day cycles of 5-fluorouracil + leucovorin + irinotecan + oxaliplatin (mFOLFIRINOX), or four (4) 21-day cycles of capecitabine+oxaliplatin (CAPOX). Participants will then receive chemo-radiation therapy according to Plan I as follows: Plan I (5 weeks): * MRI-guided pelvic IMRT to the Planning Tumor Volume (PTV) at a dose of 50 Grays (gy) delivered in 25 fractions (fx) over 5 weeks. * Concurrent chemotherapy beginning on Day 1 of RT either: * 5-FU delivered 5 or 7 days per week. * Capecitabine (Xeloda) delivered 5 days per week. After completing Plan I, participants achieving complete Clinical Response (cCR) after completing Plan I chemo-radiation will forgo the Plan II boost and continue to follow-up. Participants not achieving cCR will begin Plan II, one week after completing Plan I.

5-fluorouracil is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇪🇺 Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇨🇦 Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

🇯🇵 Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Esophageal cancer
• Anal cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Miami Miami, FL

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Patients Recruited

423,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

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.

2. England pubmed.ncbi.nlm.nih.gov

Rapid evolution in colorectal cancer: therapy now and over the next five years. [2007] A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda); Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin); Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar); Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.

3. United States pubmed.ncbi.nlm.nih.gov

A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer. [2022] Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate. Intravenous 5-fluorouracil (5-FU) and leucovorin has been a mainstay of chemotherapy, but oral 5-FU derivatives have been shown a comparable antitumor activity. Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy, drug toxicity, and quality of life.

4. Greece pubmed.ncbi.nlm.nih.gov

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.

5. Japan pubmed.ncbi.nlm.nih.gov

The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study. [2022] In this follow-up of the R-NAC-01 study, we assessed the long-term oncological benefit of four courses of modified leucovorin, 5-fluorouracil (FU), and oxaliplatin (mFOLFOX6) chemotherapy before rectal surgery.

6. Greece pubmed.ncbi.nlm.nih.gov

Retrospective Comparison of mFOLFOXIRI With XELOX/SOX as Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer. [2021] Neoadjuvant chemotherapy without radiation (NAC) shows favorable outcomes for locally advanced rectal cancer (LARC), however, the optimal regimen has not been determined yet. This study aimed to compare the efficacy and safety of oxaliplatin, irinotecan, folinic acid, and 5-fluorouracil (mFOLFOXIRI) with capecitabine/S-1 and oxaliplatin (XELOX/SOX) in rectal cancer patients.

7. Spain pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. [2020] To analyze adverse reactions in patients with nonmetastatic colorectal cancer due to treatment with either innovative or generic capecitabine and/or to the chemotherapeutic regimen employed, to the capecitabine alone, or in combination with oxaliplatin (XELOX).

8. United States pubmed.ncbi.nlm.nih.gov

Enteritis as a complication of adjuvant combination chemotherapy using 5-fluorouracil and leukovorin: clinical and helical computed tomographic features. [2022] The combination of 5-flourouracil (5-FU) and leukovorin is widely used as adjuvant chemotherapy for metastatic colorectal carcinoma. The most common clinical side effects of 5-FU are related to its gastrointestinal toxicity, chiefly stomatitis and diarrhea. The latter may be severe in up to 30% and occasionally is life-threatening. We describe a case of therapy-induced enteritis presenting as acute abdominal pain and present the computed tomographic (CT) findings. In light of the prevalence of this regimen, the potential morbidity of this complication, and a paucity of CT examples in the radiologic literature, this case illustrates an important adverse effect of this medication. Early recognition and treatment should avoid significant morbidity and mortality.

9. United States pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer. [2019] The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated.

10. United States pubmed.ncbi.nlm.nih.gov

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.