Watchful Waiting for Rectal Cancer

Overseen By Amr Aref, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Henry Ford Health System

Disqualifiers: Other cancers, Tumor location, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a non-surgical approach for treating rectal cancer. The main goal is to determine if a "watchful waiting" method, involving careful monitoring instead of immediate surgery, can effectively control cancer in patients with specific tumor types. Participants will first receive chemotherapy and radiation; if their tumors respond well, they will be carefully observed rather than undergoing immediate surgery. This trial suits adults diagnosed with rectal cancer near the anal area, particularly if surgery might cause complications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 the "Watchful Waiting" approach is likely to be safe?

Research shows that the "watchful waiting" approach for rectal cancer is safe for many patients. The German Rectal Cancer Study Group found that this method benefits those with advanced rectal cancer. It involves regular check-ups after initial treatment, without immediate surgery, and surgery occurs only if the cancer returns.

Studies have shown that patients using this method can achieve good results. The watch-and-wait approach aims to preserve the organ and avoids surgery unless absolutely necessary, leading to fewer immediate complications after treatment.

Overall, research supports the safety of this approach, focusing on reducing risks by avoiding surgery when possible and intervening only if the cancer returns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for rectal cancer, which often involve immediate surgical intervention after chemotherapy and radiation, the "watchful waiting" approach is unique because it offers a non-surgical pathway for patients showing a significant response to initial therapies. Researchers are excited about this method because it allows patients who achieve a complete or near-complete response to avoid surgery and its associated risks and complications. This approach prioritizes patient quality of life while still maintaining rigorous monitoring to ensure disease control, potentially transforming how rectal cancer is managed when a strong initial response to treatment is observed.

What evidence suggests that the "watchful waiting" approach is effective for rectal cancer?

Research has shown that "watchful waiting," an option for some participants in this trial, can benefit certain individuals with rectal cancer. This approach may be most effective for those showing no signs of cancer after initial treatments. The German Rectal Cancer Study Group found this method safe and beneficial. It involves closely monitoring the patient and initiating treatment only if the cancer returns. Many studies also indicate that this approach offers survival rates comparable to more aggressive treatments. Respected cancer guidelines support this method, suggesting it as a promising choice for suitable patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Amr Aref, MD

Principal Investigator

Ascension St. John Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with rectal cancer that's close to the anal opening and hasn't spread far (stage T3/N0-N1M0). It includes those who have a slightly less advanced stage (low T2) but need major surgery. People under 18, with other cancers, or tumors farther from the anal verge or at different stages can't join.

Inclusion Criteria

I have been diagnosed with rectal cancer.

My tumor is located very close to the end of my bowel.

I need a specific surgery for my low T2 cancer.

Exclusion Criteria

My cancer is not in the stages mentioned before.

I am under 18 years old.

I have been diagnosed with another type of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Six cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) administered every two weeks

12 weeks

6 visits (in-person)

Recovery

Recovery period following neoadjuvant chemotherapy

3 weeks

Chemo-Radiotherapy

Conventional concurrent radiation and 5FU/capecitabine treatment

7-11 weeks

Re-staging

Patients are re-staged to assess response to treatment

2-3 weeks

Watchful Waiting

Patients with complete or near complete response are monitored for local control and quality of life

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Watchful Waiting

Trial Overview

The study is testing 'watchful waiting' in patients at high risk of surgical complications. Instead of immediate radical surgery after local excision, doctors will closely monitor patients and only offer major surgery if the tumor starts growing again.

How Is the Trial Designed?

Group I: Watchful Waiting Experimental Treatment 1 Intervention

Six cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) will be administered every two weeks according to protocol. After a 3 week recovery period, this will be followed by conventional concurrent radiation and 5FU/capecitabine. Patients will be re-staged two to three weeks after completion of induction FOLFOX therapy to ensure no disease progression. The patients will be re-staged again at least 7-11 weeks post completion of nCRT. Patients with restaging results showing either complete or near complete response, will be allocated to "watchful waiting."

Watchful Waiting is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Watchful Waiting for:

• Rectal cancer with complete clinical response to neoadjuvant therapy

Approved in United States as Watchful Waiting for:

• Locally advanced rectal cancer with complete clinical response to neoadjuvant therapy

Approved in Canada as Watchful Waiting for:

• Rectal cancer with complete clinical response to neoadjuvant therapy

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Ascension South East Michigan

Lead Sponsor

Trials

19

Recruited

32,400+

Published Research Related to This Trial

In a study of 793 patients with rectal cancer who achieved a clinical complete response after neoadjuvant chemotherapy and were managed with a watch-and-wait strategy, the probability of remaining free from local regrowth was very high: 97.3% after 3 years and 98.6% after 5 years.

The study suggests that the intensity of surveillance for these patients could be safely reduced if they maintain a clinical complete response for the first 3 years, as the likelihood of remaining free from distant metastasis was also high, at 97.8% after 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study. Fernandez, LM., São Julião, GP., Figueiredo, NL., et al.[2021]

In a study of 444 patients with locally advanced rectal cancer treated by expert colorectal surgeons, the type of neoadjuvant therapy and organ preservation rates varied among surgeons, but did not impact disease-free survival rates.

The findings suggest that differing approaches to the watch-and-wait strategy among expert surgeons do not significantly affect patient survival outcomes, indicating that patient selection for this strategy can be flexible without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival. Kim, JK., Thompson, H., Jimenez-Rodriguez, RM., et al.[2023]

In a study of 324 patients with locally advanced rectal cancer, a watch-and-wait strategy after total neoadjuvant therapy resulted in organ preservation for about 50% of patients, demonstrating its potential as a viable treatment option.

The three-year disease-free survival rate was 76% for both treatment groups, indicating that this approach does not compromise survival compared to historical treatments involving surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. Garcia-Aguilar, J., Patil, S., Gollub, MJ., et al.[2023]

In a study of 35 rectal cancer patients who achieved clinical complete response (cCR) or near-cCR after neoadjuvant chemoradiotherapy, an organ preservation strategy resulted in an impressive organ-preservation rate of 88.6% and a sphincter-preservation rate of 97.1%.

The approach demonstrated excellent cancer-specific survival (100%) and overall survival (92.7%) rates, suggesting that this strategy can effectively improve quality of life for patients while providing a viable alternative to standard surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Outcome of watch and wait strategy or organ preservation for rectal cancer following neoadjuvant chemoradiotherapy: report of 35 cases from a single cancer center]. Wu, A., Wang, L., Du, C., et al.[2018]

Patients with locally advanced rectal cancer who followed a watch-and-wait strategy after neoadjuvant therapy reported significantly better bowel function compared to those who underwent sphincter-preserving surgery, with a median total score of 76 versus 55 (p < 0.001).

The greatest improvement in bowel function for the watch-and-wait group was observed in the urgency/soilage subscale, indicating that this nonoperative approach may lead to fewer bowel control issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Bowel Function in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy After Neoadjuvant Therapy: A Case-Control Study. Quezada-Diaz, FF., Smith, JJ., Jimenez-Rodriguez, RM., et al.[2022]

In a study comparing 26 patients using a watch and wait strategy after neoadjuvant treatment to 22 patients who underwent surgery after achieving a pathological complete response, both groups showed similar oncological outcomes, indicating that surgery can be safely deferred for clinical complete responders.

The study found no significant differences in local or distant recurrence rates, disease-free survival (87.9% for watch and wait vs. 80% for surgery), or overall survival (86% for watch and wait vs. 85% for surgery), suggesting that nonoperative management is a viable option for patients with low rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer. Coraglio, MF., Eleta, MA., Kujaruk, MR., et al.[2021]

The watch-and-wait approach for rectal cancer patients who achieve a clinical complete response after neoadjuvant chemoradiation shows a 2-year local regrowth rate of 15.7%, with 95.4% of those experiencing regrowth successfully treated with salvage therapies.

There were no significant differences in cancer-specific mortality or overall survival between patients managed with watch-and-wait and those who underwent surgery, suggesting that watch-and-wait could be a safe alternative, although more extensive studies are needed to confirm long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Dossa, F., Chesney, TR., Acuna, SA., et al.[2022]

Patients with locally advanced rectal cancer who followed a watch-and-wait policy after achieving a complete response to chemoradiation reported better quality of life outcomes compared to those who underwent total mesorectal excision, with improvements in physical and cognitive function, emotional roles, and overall health status.

Despite some long-term side effects from chemoradiation, the watch-and-wait approach resulted in fewer issues related to defecation, sexual function, and urinary tract function, suggesting it may be a preferable option for select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection - A Matched-Controlled Study. Hupkens, BJP., Martens, MH., Stoot, JH., et al.[2019]

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