Combination Chemotherapy + Radiation for Rectal Cancer

Overseen By Vincent Basehart

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Active malignancy, Metastatic disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a short course of radiation therapy followed by a combination of chemotherapy drugs for individuals with stage II-III rectal cancer. The goal is to determine if this combined approach can shrink tumors and reduce the need for surgery, potentially improving quality of life. The trial includes treatment with radiation and various chemotherapy drugs, such as capecitabine (Xeloda) and fluorouracil (5-FU). It seeks participants diagnosed with stage II or III rectal cancer that has not spread to other parts of the body. If this matches your condition, this trial might be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that Intensity-Modulated Radiation Therapy (IMRT) had a high success rate, with 99.6% of patients completing the treatment. Only one patient stopped due to diarrhea, and no severe toxic reactions occurred. IMRT is generally well-tolerated.

Research indicates that the chemotherapy combination mFOLFOX6, which includes oxaliplatin, fluorouracil, and leucovorin, effectively treats colorectal cancer. The FDA has approved these drugs, confirming their general safety, though they can cause side effects like nausea or tiredness.

The CapeOX combination, using capecitabine and oxaliplatin, has also proven effective for colorectal cancer. However, some patients experienced serious digestive issues like diarrhea. Despite this, the combination is considered safe for many patients.

Overall, these treatments have been used in other studies, demonstrating they are mostly well-tolerated. However, as with any treatment, there are some risks of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for rectal cancer because it combines cutting-edge Intensity-Modulated Radiation Therapy (IMRT) with chemotherapy regimens that include oxaliplatin, fluorouracil, and capecitabine. Unlike the traditional approach of just surgery and chemotherapy, this treatment regimen uses IMRT to precisely target tumors, potentially reducing side effects and sparing healthy tissue. The addition of oxaliplatin and capecitabine could enhance the effectiveness of the chemotherapy, offering a more powerful way to attack cancer cells. This combination may lead to quicker and more complete tumor shrinkage, allowing for less invasive treatments or even non-operative management for patients showing complete clinical response.

What evidence suggests that this trial's treatments could be effective for rectal cancer?

In this trial, participants will receive Intensity-Modulated Radiation Therapy (IMRT). Previous studies have found that IMRT causes fewer severe side effects than traditional radiation methods, potentially making it more comfortable for patients. For chemotherapy, participants may receive mFOLFOX6, which research has shown helped 71.6% of patients remain cancer-free for at least three years. Alternatively, some participants may receive CapeOX (capecitabine and oxaliplatin), which has shown promising results, particularly for patients with mid-to-low rectal cancer, by either shrinking tumors or preventing the cancer from spreading. ^{6 7 8 9 10}

Who Is on the Research Team?

Ann Raldow, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Intensity-Modulated Radiation Therapy
• Leucovorin
• Oxaliplatin
• Total Mesorectal Excision

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (IMRT, mFOLFOX6, CapeOX, TME) Experimental Treatment 8 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:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

The Joseph Drown Foundation

Collaborator

Trials

1

Recruited

30+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Published Research Related to This Trial

5-fluorouracil (5-FU) remains a key chemotherapy drug for colorectal cancer, but its oral form was previously abandoned due to inconsistent absorption; however, Xeloda (capecitabine) offers a solution by being an orally administered drug that is selectively activated in tumors, leading to higher local concentrations of 5-FU.

In phase II clinical trials for colorectal cancer, Xeloda demonstrated response rates of 21-24% and a median time to disease progression of 127-230 days, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluoropyrimidines: a critical evaluation. Brito, RA., Medgyesy, D., Zukowski, TH., et al.[2017]

The Phase I study determined that the maximal tolerated dose of capecitabine combined with standard radiotherapy for rectal cancer is 1600 mg/m²/day, which is important for future treatment protocols.

Dose-limiting toxicities were observed at lower doses, including Grade 3 diarrhea and skin toxicity, indicating that while capecitabine can be effective, careful monitoring for side effects is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. Souglakos, J., Androulakis, N., Mavroudis, D., et al.[2019]

Preoperative radiotherapy combined with oral capecitabine has shown promising results in increasing tumor down-staging and the likelihood of sphincter-sparing surgeries, with a pathological complete response rate of up to 31% in some trials.

Capecitabine, taken orally, may offer a safer alternative to intravenous 5-fluorouracil, as it reduces the risk of complications associated with long-term venous access, although it can cause mild to moderate side effects like hand-foot syndrome and leukopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and oral capecitabine in the preoperative treatment of patients with rectal cancer: rationale, preliminary results and perspectives. Corvò, R., Pastrone, I., Scolaro, T., et al.[2022]

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

In a study of 110 patients with advanced rectal cancer, the combination of preoperative radiotherapy and XELOX (capecitabine and oxaliplatin) resulted in a pathologic complete response (pCR) rate of 16%, indicating significant tumor reduction before surgery.

The treatment was generally feasible, with 95% of patients achieving R0 resections, although 43% experienced postoperative complications, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. Rödel, C., Liersch, T., Hermann, RM., et al.[2022]

Capecitabine, an oral fluoropyrimidine, has been shown to achieve superior response rates and equivalent overall survival compared to traditional intravenous 5-FU plus leucovorin in metastatic colorectal cancer, making it a preferred treatment option.

Recent trials, including the Xeloda Adjuvant Chemotherapy Trial (X-ACT), confirm that capecitabine is at least as effective and safer than IV 5-FU/LV for adjuvant treatment in patients with resected stage III colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine: bridging the Atlantic divide in colon cancer treatment. Van Cutsem, E., Verslype, C., Tejpar, S.[2018]

In a study of 11 patients with locally advanced rectal cancer, the combination of oral 5-doxifluridine (5-dFUR) and l-leucovorin with pelvic radiotherapy resulted in two patients achieving pathologically complete remission after treatment, indicating potential effectiveness in improving tumor response.

The treatment was generally well-tolerated, with manageable side effects such as grade 3 diarrhea in one patient and mild nausea and vomiting in three, while no significant hematological toxicity was observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated treatment with doxifluridine and radiotherapy in recurrent or primary unresectable rectal cancer. A feasibility study. Di Bartolomeo, M., Bajetta, E., Buzzoni, R., et al.[2022]

In a study of 65 patients with rectal adenocarcinoma, pre-operative radiotherapy combined with oral tegafur-uracil (UFUR) and leucovorin (LV) resulted in significant tumor downstaging in 75% of patients and a pathological complete response in 25%.

The treatment showed a high 3-year overall survival rate of 92% and manageable toxicity, with only 9% of patients experiencing severe diarrhea and 3% experiencing severe leucopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer. Wang, LW., Yang, SH., Lin, JK., et al.[2013]

In a phase II study involving 54 patients with locally advanced rectal cancer, the combination of capecitabine and radiotherapy resulted in a pathologic complete response rate of 18% and a significant downstaging of tumors in 51% of patients, indicating its efficacy as a neoadjuvant treatment.

The treatment was well tolerated, with manageable side effects, and showed a sphincter preservation rate of 67% for tumors located close to the anal verge, making it a convenient alternative to traditional 5-FU infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Krishnan, S., Janjan, NA., Skibber, JM., et al.[2022]

In a study involving 67 patients with stage II and III rectal adenocarcinoma, capecitabine was found to be at least as effective as 5-Fluorouracil in adjuvant chemoradiotherapy, with no significant differences in toxicity or overall survival rates.

There was a notable trend towards improved loco-regional recurrence-free survival in patients treated with capecitabine, suggesting it may work better in combination with radiotherapy compared to 5-Fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer. Kurt, M., Ozkan, L., Kurt, E., et al.[2015]

Citations

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Phase II study of capecitabine plus oxaliplatin (CapOX) as ... Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.90

Real-world assessment of capecitabine and oxaliplatin ... Dose reductions for oxaliplatin and capecitabine were observed in 37% (57/153) and 39% (59/153) of patients, respectively. Hospitalizations ...

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Long-term outcomes of a prospective trial (PKUCH-R03 trial) For patients with mid-low rectal cancer with negative MRF, 3 months of NCT were found to yield a favorable tumor response with acceptable toxicity.

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Postoperative Chemoradiotherapy With Capecitabine and ... This randomized clinical trial examines the efficacy and toxic effects of postoperative capecitabine vs oxaliplatin plus capecitabine with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1533002825000271

Treatment Adherence to Adjuvant Chemotherapy ... One out of 5 patients did not complete 4 cycles of CAPOX. The overall mean RDI of adjuvant treatment was 82.9% (± 23.5) for capecitabine and 83.8% (± 22.5) for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7842523/

Efficacy and Safety of Capecitabine and Oxaliplatin ... CapOX therapy as an adjuvant chemotherapy for groups at high risk of recurrence of stage II and stage III colon cancer has been demonstrated to be excellent.

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Efficacy and Safety of Oxaliplatin Combined With ... The study aims to identify the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with local advanced colorectal cancer. Conditions.

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The safety of four cycles of CAPEOX combined with ... The safety of four cycles of CAPEOX combined with radiotherapy vs. capecitabine combine with radiotherapy for locally advanced rectal cancer: ...

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Concurrent oxaliplatin, capecitabine, and radiation therapy ... This treatment was associated with a high rate of GI toxicity with 30% of patients developing grade 3 or 4 diarrhea and one toxic death. We argue that this dose ...

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Oxaliplatin combined with capecitabine therapy and ... Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients.