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

Trial Summary

What is the purpose of this trial?

This trial uses a combination of chemotherapy and radiation therapy before surgery for patients with rectal cancer. The goal is to improve their response to treatment by killing cancer cells and shrinking tumors. The trial uses UFT and leucovorin, which have shown encouraging preliminary results as an alternative to the conventional 5-FU in preoperative chemoradiation for rectal cancer.

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.

What data supports the effectiveness of the treatment combination of chemoradiation (capecitabine and radiation) + FOLFOXIRI (Oxaliplatin, leucovorin, irinotecan, and fluorouracil) for rectal cancer?

Research shows that preoperative chemoradiation with capecitabine and radiation is effective in reducing local recurrence of rectal cancer. Additionally, the FOLFOXIRI combination has shown improved outcomes in advanced colorectal cancer, suggesting potential benefits when used together with chemoradiation for rectal cancer. ^{1 2 3 4 5}

Is the combination of chemoradiation and FOLFOXIRI safe for humans?

The combination of chemoradiation (capecitabine and radiation) and FOLFOXIRI (oxaliplatin, leucovorin, irinotecan, and fluorouracil) has been studied for safety in various trials. Studies have shown that these treatments can be safe, but they may have side effects, and their safety profile should be evaluated further in larger studies. ^{5 6 7 8 9}

How is the treatment of preoperative chemoradiation plus FOLFOXIRI for rectal cancer different from other treatments?

This treatment is unique because it combines chemoradiation (capecitabine and radiation) with FOLFOXIRI (a mix of oxaliplatin, leucovorin, irinotecan, and fluorouracil), aiming to enhance tumor response before surgery. The addition of oxaliplatin and irinotecan to the standard chemoradiation regimen is intended to improve outcomes, although it may increase toxicity. ^{4 5 10 11 12}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy of rectal cancer new treatment perspectives. [2022]

2. England pubmed.ncbi.nlm.nih.gov

FOLFOXIRI plus biologics in advanced colorectal cancer. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Oxaliplatin and preoperative chemoradiotherapy in rectal cancer]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant capecitabine, oxaliplatin, and irinotecan (XELOXIRI) in patients with locally advanced rectal cancer. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Survival benefit and safety of the combinations of FOLFOXIRI ± bevacizumab versus the combinations of FOLFIRI ± bevacizumab as first-line treatment for unresectable metastatic colorectal cancer: a meta-analysis. [2022]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. [2022]

12. Thailand pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX followed by Chemoradiotherapy for Middle and Lower Rectal Cancer. [2021]