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

Trial Summary

What is the purpose of this trial?

This pilot trial studies how well active surveillance and chemotherapy before surgery work in treating participants with stage II-III rectal cancer. Active surveillance involves monitoring participants for additional tumor growth after receiving cancer treatment. Drugs used in chemotherapy 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. It is not yet known whether deferring surgery after active surveillance and chemotherapy will work better in treating participants with stage II-III rectal cancer.

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.

What data supports the effectiveness of the treatment for rectal cancer?

Research shows that chemotherapy, when combined with radiation therapy before surgery, can significantly reduce the risk of cancer coming back in the same area. Even a partial response to this pre-surgery treatment is linked to lower chances of the cancer spreading to other parts of the body. ^{1 2 3 4 5}

Is pre-surgery chemotherapy for rectal cancer safe for humans?

Pre-surgery chemotherapy for rectal cancer has been studied for safety, showing some common side effects like low blood cell counts, diarrhea, and nausea. These side effects are generally manageable, but severe cases can occur, so it's important to be monitored by healthcare professionals during treatment. ^{6 7 8 9 10}

How is pre-surgery chemotherapy for rectal cancer different from other treatments?

Pre-surgery chemotherapy for rectal cancer is unique because it is given before surgery to shrink the tumor and reduce the risk of cancer spreading, which can improve the chances of successful surgery and lower the chance of cancer coming back. ^{2 11 12 13 14}

Research Team

George J. Chang

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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 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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy and rectal cancer]. [2018]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival. [2005]

4. Germany pubmed.ncbi.nlm.nih.gov

Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity? [2021]

5. England pubmed.ncbi.nlm.nih.gov

Emerging therapies for rectal cancer. [2007]

6. Greece 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. [2018]

7. England 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). [2013]

8. Greece 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. [2019]

9. England 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? [2014]

10. Greece pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy with 5-fluorouracil/leucovorin, surgery and adjuvant chemotherapy for locally advanced rectal cancer. [2021]

11. United States 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. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Analysis of Survival in Complete Pathological Response after Long-Course Chemoradiotherapy in Patients with Advanced Rectal Cancer. [2023]

13. Japan pubmed.ncbi.nlm.nih.gov

[Treatment Strategy for Stage Ⅳ Rectal Cancer]. [2015]

14. Italy pubmed.ncbi.nlm.nih.gov

[Postoperative chemotherapy in rectal carcinoma]. [2006]