Preoperative Chemoradiation + FOLFOXIRI for Rectal Cancer

Recruiting at 4 trial locations

Overseen By Patrick M Boland, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Pregnancy, Prior invasive malignancy, Severe comorbidity, 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

Compensation: Varies

Number of Visits: 1

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for rectal cancer, combining chemotherapy and radiation before surgery. The goal is to determine the safety and effectiveness of this treatment in shrinking tumors and improving outcomes. Participants will receive chemoradiation (capecitabine and radiation) combined with FOLFOXIRI (a chemotherapy regimen including oxaliplatin, leucovorin, irinotecan, and fluorouracil) to assess if it leads to a complete response before surgery. Individuals diagnosed with rectal cancer, specifically adenocarcinoma that hasn't spread to distant sites, and who can carry on daily activities, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on therapeutic anticoagulation (blood thinners), you may participate if you have been stable on the medication for at least two weeks.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that combining treatments, such as chemoradiation with capecitabine and a drug mix called FOLFOXIRI (including oxaliplatin, leucovorin, irinotecan, and fluorouracil), is generally well-tolerated by patients. Studies have found that using capecitabine and irinotecan before surgery is safe, with manageable side effects. Another study found that a similar treatment, FOLFOX, can be safely administered after chemoradiation for rectal cancer.

In simple terms, while side effects may occur, the treatment is considered safe for patients. Most people tolerate it well, and researchers closely monitor safety throughout the trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for rectal cancer?

Researchers are excited about this treatment for rectal cancer because it combines chemoradiation with a powerful chemotherapy regimen known as FOLFOXIRI. Unlike standard treatments that might use these approaches separately, this combination is designed to maximize cancer cell destruction before surgery. By using capecitabine with radiation and adding the potent mix of oxaliplatin, leucovorin, irinotecan, and fluorouracil, the treatment aims to shrink tumors more effectively and improve surgical outcomes. This integrative approach could potentially enhance patient survival rates and reduce the likelihood of cancer returning.

What evidence suggests that this treatment might be an effective treatment for rectal cancer?

Research shows that combining chemoradiation with a treatment called FOLFOXIRI may hold promise for rectal cancer. In this trial, participants will receive an experimental combination of chemoradiation (capecitabine and radiation) and FOLFOXIRI (oxaliplatin, leucovorin, irinotecan, and fluorouracil) before surgery. One study found that 77.9% of patients who underwent chemoradiotherapy received additional chemotherapy, with many receiving treatments similar to FOLFOX. Another study demonstrated that using irinotecan with drugs like oxaliplatin and capecitabine can effectively combat cancer. The aim is to shrink tumors before surgery, potentially leading to better outcomes. Early findings suggest that this combination might improve survival rates and help prevent cancer from spreading. ^{2 6 7 8 9}

Who Is on the Research Team?

Salma Jabbour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Patrick M Boland, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

Adults over 18 with stage T3 or T4 rectal cancer without distant metastases, good organ function, and no severe comorbidities. They must not have had previous chemotherapy for colorectal cancer, be free from other active cancers for three years, and not have certain infections or uncontrolled diseases. Women of childbearing potential need a negative pregnancy test and agree to contraception; men also need to use contraception.

Inclusion Criteria

Zubrod Performance Status 0-2

Be willing and able to provide written informed consent for the trial

No active second cancers

Exclusion Criteria

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of three years

Prior radiotherapy to the region of your present study cancer that would result in overlap of radiation therapy fields

Severe, active comorbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last twelve months Transmural myocardial infarction within the last six months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake Known, existing uncontrolled coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least two weeks

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemoradiation

Participants receive chemoradiation (capecitabine and radiation) for 28 days

4 weeks

FOLFOXIRI Treatment

Participants receive FOLFOXIRI (Oxaliplatin, leucovorin, irinotecan, and fluorouracil) for 8 cycles prior to surgery

16 weeks

Safety Follow-up

Participants receive safety follow-up assessments approximately 30 and 90 days after treatment discontinuation

3 months

Survival Follow-up

Participants are followed for survival every three months until death, withdrawal of consent, or study completion

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Combination of drugs (chemoradiation (capecitabine and radiation) + FOLFOXIRI (Oxaliplatin, leucovorin, irinotecan, and fluorouracil))

Trial Overview The trial tests preoperative chemoradiation combined with FOLFOXIRI (a mix of Oxaliplatin, leucovorin, irinotecan, fluorouracil) in rectal cancer patients. Participants will receive this treatment before surgery to assess safety and effectiveness in increasing complete response rates.

How Is the Trial Designed?

Group I: Combination of drugs prior to surgery Experimental Treatment 1 Intervention

Receive the experimental combination of drugs (chemoradiation (capecitabine and radiation) + FOLFOXIRI (Oxaliplatin, leucovorin, irinotecan, and fluorouracil) prior to surgery and undergo laboratory tests and study procedures on specified days during the study period, complete end of study evaluations and tests, and participate in post-study follow up every three months for three to four years. The time in the study will take approximately four - six hours during pre-study, study and end of study visits.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Published Research Related to This Trial

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]

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

The combination of FOLFOXIRI (oxaliplatin, irinotecan, fluorouracil, and leucovorin) with the biologic agent panitumumab has shown improved outcomes in metastatic colorectal cancer (mCRC) patients, based on randomized clinical trial results.

While FOLFOXIRI combined with bevacizumab has extensive data from large trials, its true benefit is still uncertain as it hasn't been tested in a randomized setting, highlighting the need for further research to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI plus biologics in advanced colorectal cancer. García-Alfonso, P., Torres, G., García, G., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25446610/

Efficacy endpoints of radiation therapy group protocol 0247 Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303269

Preoperative Treatment of Locally Advanced Rectal Cancer In the chemoradiotherapy group, 423 of 543 patients (77.9%) received adjuvant chemotherapy; 281 of these 423 patients (66.4%) received FOLFOX ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419366967

Chronicle: results of a randomised phase III trial in locally ... Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 ...

4. academic.oup.com academic.oup.com/jnci/article/107/11/djv248/2457689

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or ... The three-year rate of local events in the oxaliplatin group was 24.1% compared with 19.2% in the nonoxaliplatin group. Three-year event rate ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1356708/full

The effective combination therapies with irinotecan for ... Irinotecan is a comprehensive anticancer therapy when combined with other drugs, such as oxaliplatin, capecitabine, 5-fluorouracil (5-FU) and leucovorin.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2361227/

Concurrent chemoradiation with capecitabine and weekly ... The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2006.24.18_suppl.3526

ECOG E3201: Intergroup randomized phase III study of ... E3201 provides important comparative toxicity information demonstrating that FOLFOX can be safely administered to rectal cancer pts following chemoradiation.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301610000295

Preoperative Chemoradiation With Irinotecan and ... Our results indicate that preoperative CRT with irinotecan and capecitabine is safe and effective with well-tolerated toxicity profiles, with a promising pCR ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9306070/

Safety and efficacy of irinotecan, oxaliplatin, and capecitabine ... We showed that the use of the XELOXIRI regimen, which involves the replacement of 5-fluorouracil with capecitabine, is well tolerated and safe.