Pre-Surgery Chemotherapy for Rectal Cancer

Overseen By George J. Chang

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Inflammatory bowel disease, MSI-H colorectal, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether chemotherapy before surgery, combined with active monitoring, effectively treats stage II-III rectal cancer. Chemotherapy stops cancer cells from growing or spreading. The researchers aim to determine if delaying surgery after chemotherapy, along with close observation, could be beneficial. Participants with rectal cancer located less than 12 cm from the anal verge and no prior pelvic radiation might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking 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 team or your doctor.

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

Research has shown that chemotherapy can cause side effects in people with rectal cancer. One study found that 45.7% of patients experienced moderate-to-severe side effects. Common issues included stomach problems, nerve issues, and low white blood cell counts, which can hinder the body's ability to fight infections. Despite these serious side effects, chemotherapy remains a common cancer treatment because it can stop cancer cells from growing and spreading.

Another study found that patients with rectal cancer who received chemotherapy before surgery had better outcomes. Although the treatment can be challenging, many patients benefit from it over time. It is important to weigh the potential risks and benefits and discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a potentially game-changing approach for treating rectal cancer. Unlike the traditional path of immediate surgery following chemotherapy, this trial includes an option for active surveillance after chemotherapy. If a patient's cancer responds well, they might avoid surgery entirely, as long as the cancer doesn't progress, which could lead to fewer side effects and a better quality of life. This type of personalized treatment plan is what has researchers hopeful for better outcomes and more tailored care for patients.

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

Research shows that chemotherapy can effectively treat rectal cancer. In this trial, participants will be divided into two groups. Group I will undergo standard surgical resection, while Group II will receive active surveillance and consolidated chemotherapy for up to 4 months, with surgical resection if necessary. Studies indicate that patients who receive chemotherapy before surgery, known as preoperative treatment, tend to have high survival rates. For instance, one study found that about 81% of patients who received a specific chemotherapy plan called FOLFOX were disease-free after five years. Another study revealed that patients who had additional chemotherapy after their main treatment, called adjuvant chemotherapy, had a five-year overall survival rate of 65.8%, higher than those who did not receive it. These findings suggest that chemotherapy can improve survival and lower the chance of cancer returning. ^{4 5 6 7 8}

Who Is on the Research Team?

George J. Chang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage II-III rectal cancer who can undergo standard chemotherapy and are fit enough for potential surgery. They must have measurable disease, be able to use contraception if needed, and provide consent. Excluded are those with bowel obstruction, inability to undergo MRI, certain genetic cancer types like MSI-H, prior pelvic radiation or active treatment for other cancers.

Inclusion Criteria

My diagnosis is rectal cancer confirmed by tissue examination.

My cancer can be measured or seen on scans.

My rectal cancer can be surgically removed with the goal of curing it.

Exclusion Criteria

I am not currently receiving treatment for another cancer that would interfere with this trial's treatment.

I have had radiation therapy to my pelvic area before.

I cannot or do not want to have a pelvic MRI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive chemoradiation treatment to achieve clinical complete response

4 months

Active Surveillance and Consolidated Chemotherapy

Participants receive active surveillance and consolidated chemotherapy in the absence of disease progression or unacceptable toxicity

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Group I: 6 and 12 months, then annually for 3 years; Group II: every 3 months for 18 months, every 6 months for 2 years, then annually for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Resection of Rectum

Trial Overview The study tests the effectiveness of monitoring tumor growth (active surveillance) combined with pre-surgery chemotherapy in treating rectal cancer patients. It aims to determine if delaying surgery after these treatments leads to better outcomes compared to immediate surgery.

How Is the Trial Designed?

Group I: Group II (active surveillance) Experimental Treatment 4 Interventions

Participants who have achieved clinical complete response receive active surveillance and consolidated chemotherapy for up to 4 months in the absence of disease progression or unacceptable toxicity. Participants with incomplete response or regrowth of tumor, undergo surgical resection as in Group I.

Group II: Group I (surgical resection) Active Control 2 Interventions

Participants who have achieved clinical complete response undergo standard surgical resection.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

For patients with rectal carcinoma staged pT3 or with involved lymph nodes, concurrent chemoradiation is recommended as an effective adjuvant treatment to control local disease and prevent metastases.

While the role of chemotherapy remains uncertain, it appears beneficial for patients with pathological B2 or C stage after preoperative chemoradiation, suggesting that adjuvant chemotherapy should be considered in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative chemotherapy in rectal carcinoma]. Cionini, L., Falcone, A.[2006]

In a study of 1033 colorectal cancer patients treated with 5-fluorouracil (5FU) based adjuvant therapy, certain adverse events like neutropenia, nausea/vomiting, and mucositis were linked to better disease-free survival (DFS) and overall survival (OS).

Patients who experienced any grade of neutropenia had a 19% lower risk of disease progression, while those with nausea/vomiting had a 38% lower risk of death, suggesting that these adverse effects may serve as positive indicators of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of adverse events and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil and leucovorin: Is efficacy an impact of toxicity? Soveri, LM., Hermunen, K., de Gramont, A., et al.[2014]

In a study of 48 patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy using the FOLFOX regimen, 50% showed a positive histopathological response, which included both complete and partial responses.

Patients who responded to chemotherapy had a significantly better 3-year disease-free survival rate of 86% compared to 62% for nonresponders, highlighting the importance of tumor response in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Even a partial pathological response is associated with lower relapse rates in patients with operable rectal cancer undergoing neoadjuvant chemotherapy. Koizumi, M., Yamada, T., Shinji, S., et al.[2021]

In a study of 1442 patients with locally advanced rectal cancer, adjuvant chemotherapy (AC) after preoperative chemoradiation therapy did not significantly improve relapse-free or overall survival rates compared to observation alone.

The addition of oxaliplatin to 5-fluorouracil (5-FU) in AC showed no significant benefit in survival outcomes, indicating that 5-FU-based AC may not be effective following surgery and preoperative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study. Chung, MJ., Lee, JH., Lee, JH., et al.[2019]

In a study of 154 patients with advanced rectal cancer, only 18.8% achieved a complete pathological response after neoadjuvant chemoradiotherapy, which is crucial for improving survival rates.

Patients with high tumor regression grade scores (TRG0 and TRG1) had a significantly better survival rate of over 90%, highlighting the importance of tumor response in predicting outcomes after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Survival in Complete Pathological Response after Long-Course Chemoradiotherapy in Patients with Advanced Rectal Cancer. Ulusoy, C., Kamalı, GH., Nikolovski, A.[2023]

Surgery remains the most effective treatment for rectal cancer, but it only cures about 50% of patients, highlighting the need for additional therapies.

Combining radiation therapy with chemotherapy after surgery has shown a synergistic effect that improves survival rates, suggesting that this approach may be a key strategy in future rectal cancer treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival. Sexe, R., Miedema, BW.[2005]

Chemotherapy does not extend survival for rectal cancer patients, but it significantly reduces the risk of local recurrence when combined with radiotherapy.

Achieving a complete pathological response (sterilization of the tumor) through chemotherapy is a positive prognostic factor, and new trials are exploring effective drug combinations to enhance these response rates before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy and rectal cancer]. Michel, P., Di Fiore, F.[2018]

In a study of 59 patients with advanced rectal cancer, preoperative intensified chemoradiotherapy led to a significant rate of pathological complete responses, with 20.3% showing no residual cancer cells after treatment.

While intensified treatment improved cancer response, it also resulted in a higher incidence of surgical complications, particularly in patients with major tumor responses, highlighting the need for careful management during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity? Horisberger, K., Hofheinz, RD., Palma, P., et al.[2021]

In a study of 18 patients with cStage IV rectal cancer who received preoperative chemotherapy, 10 patients showed a partial response and 8 had stable disease, indicating that chemotherapy can have a significant antitumor effect before surgery.

While there was no significant difference in overall survival compared to patients who did not receive chemotherapy, those who underwent preoperative treatment had a higher rate of curability (44.4% vs. 26.7%), suggesting that it may improve surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment Strategy for Stage Ⅳ Rectal Cancer]. Sakamoto, Y., Morohashi, H., Yoshida, E., et al.[2015]

Preoperative treatment with short-course radiotherapy or chemo-radiotherapy is commonly used to reduce local recurrence in operable rectal cancer, but there is a need for improved strategies to enhance patient survival.

Research into combining chemotherapy agents like oxaliplatin and irinotecan with targeted therapies such as bevacizumab and cetuximab is ongoing, aiming to develop new treatment options that can be tailored to individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for rectal cancer. Chua, YJ., Cunningham, D.[2007]

Neoadjuvant chemotherapy using modified OPTIMOX1 combined with bevacizumab was administered to 10 patients with advanced rectal cancer, showing a manageable safety profile with only one case of grade 2 leukopenia and no significant neurotoxicity.

The treatment resulted in significant downstaging of tumors, with 20% of patients experiencing primary tumor downstaging and 70% node downstaging, suggesting that this chemotherapy regimen may enhance the feasibility of radical or anus-preserving surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Preoperative Chemotherapy with Modified OPTIMOX-1 Plus Bevacizumab in Patients with Advanced Rectal Cancer with Factors Contraindicative of Curative Surgery. Kosugi, C., Koda, K., Tanaka, K., et al.[2018]

A multicentre Phase II study is underway to assess the safety and efficacy of neoadjuvant chemoradiotherapy using the drug S-1 in 35 patients with locally advanced rectal cancer, aiming to improve treatment outcomes compared to standard practices in Japan.

The study will evaluate key endpoints such as the rate of complete treatment, response rates, and short-term clinical outcomes, including adverse events and surgery-related complications, to determine the potential benefits of this new treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective feasibility study to evaluate neoadjuvant-synchronous S-1 + RT for locally advanced rectal cancer: a multicenter phase II trial (UMIN ID: 03396). Inomata, M., Akagi, T., Nakajima, K., et al.[2013]

In a study of 28 patients with node-positive colorectal cancer (NP-CRC) and 15 patients with node-positive gastric cancer (NP-GC), the quality of life (QOL) after chemotherapy showed no significant differences between the two groups.

However, NP-CRC patients experienced more hematological adverse events, such as mild leucopenia, and higher treatment costs compared to NP-GC patients, indicating a greater burden associated with NP-CRC chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical comparison of QOL and adverse events during postoperative adjuvant chemotherapy in outpatients with node-positive colorectal cancer or gastric cancer. Mukai, M., Kishima, K., Uchiumi, F., et al.[2019]

In a study of 71 patients with locally advanced rectal cancer, preoperative chemoradiotherapy using 5-fluorouracil (5-FU) and leucovorin achieved a pathologic complete response (pCR) rate of 14.1%, exceeding the target of 10%.

The treatment resulted in a low local relapse rate of 6.1% and favorable long-term outcomes, with 5-year disease-free survival at 54% and overall survival at 68%, although it was associated with some adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer. Baur, M., Horvath, M., Stättner, S., et al.[2021]

Citations

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Preoperative Treatment of Locally Advanced Rectal Cancer Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy ...

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Total neoadjuvant therapy in rectal cancer Current management of locally advanced rectal cancer achieves high cure rates, distant metastatic spread being the main cause of patients' ...

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The Impact of Adjuvant Chemotherapy on Clinical ... Adjuvant chemotherapy remains an open question in the treatment of locally advanced rectal cancer, with conflicting data on the benefit to patient outcomes.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37049-8/fulltext

Patients with rectal cancer receiving adjuvant ... The 5-year overall survival was 65.8% [95% confidence interval (CI) 50–84] for patients having adjuvant chemotherapy compared with 45.6% (95% CI 39–52) for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11274507/

Chemotoxicity and Associated Risk Factors in Colorectal Cancer The study found that 45.7% of patients experienced overall moderate-to-severe toxicities, with gastrointestinal toxicity (22.9%) and neuropathy or neutropenia ...

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Long-Term Outcome of Rectal Cancer Patients Treated by ... The median follow-up duration was 66 (range, 10–161) months. The 3- and 5-year overall survival (OS) rates for all patients were 90.5% and 72.7%, respectively.

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2800128

Trends in the Characteristics, Treatment, and Outcomes of ... The use of neoadjuvant chemoradiotherapy has also improved the outcomes of rectal cancer significantly. Two major clinical trials concluded the ...