What side effects are associated with this type of intervention?

Common treatments for rectal cancer, such as FOLFIRINOX, FOLFOX, and CAPOX, often involve a combination of fluorouracil, irinotecan, leucovorin, and oxaliplatin. The known side effects of these treatments include severe neutropenia, neuropathy, diarrhea, nausea, vomiting, fatigue, and hand-foot syndrome. Specifically, oxaliplatin is associated with cumulative sensory neuropathy, and irinotecan can cause significant gastrointestinal toxicity, including severe diarrhea. These side effects can vary in severity and may require dose adjustments or supportive care to manage.

What prior FDA approvals exist?

The FDA has approved several treatments for rectal cancer, particularly focusing on chemotherapy regimens that include drugs like Irinotecan, a Topoisomerase I Inhibitor. Irinotecan is often used in combination with other chemotherapeutic agents such as fluorouracil and leucovorin, forming regimens like FOLFIRI (fluorouracil, leucovorin, and irinotecan). Additionally, oxaliplatin-based regimens like FOLFOX (fluorouracil, leucovorin, and oxaliplatin) and CAPOX (capecitabine and oxaliplatin) are also commonly used. These combinations aim to enhance the efficacy of treatment by targeting cancer cells through multiple mechanisms.

What other types of research exist?

Promising novel alternatives to Irinotecan for rectal cancer patients include: 1) FOLFOX (combination of leucovorin, fluorouracil, and oxaliplatin), which is used after chemoradiation and may increase response rates. 2) CAPOX (combination of capecitabine and oxaliplatin), another effective regimen post-chemoradiation. 3) FOLFIRINOX (combination of fluorouracil, irinotecan, leucovorin, and oxaliplatin), which has shown potential in increasing clinical complete response rates and organ preservation. These alternatives are being studied for their efficacy and safety in comparison to traditional Irinotecan-based treatments.

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Alkylating agent

Irinotecan + FOLFOX Chemotherapy for Rectal Cancer (JANUS Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for rectal cancer, such as FOLFOX (fluorouracil, leucovorin, oxaliplatin) and CAPOX (capecitabine, oxaliplatin), work through various mechanisms to inhibit tumor growth. Fluorouracil and capecitabine are antimetabolites that interfere with DNA synthesis, preventing cancer cells from dividing. Oxaliplatin is a platinum-based drug that causes DNA crosslinking, leading to cell death. Irinotecan, a topoisomerase I inhibitor, prevents DNA unwinding, which is crucial for replication and transcription. These mechanisms are vital for rectal cancer patients as they target different aspects of cancer cell proliferation, increasing the likelihood of treatment success and potentially improving outcomes.

Phase 2

Recruiting

Research Sponsored by Alliance for Clinical Trials in Oncology

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing different treatments in patients with advanced rectal cancer to see which one is more effective at shrinking the tumor or stopping its growth, potentially avoiding surgery.

Who is the study for?

This trial is for adults with stage II-III rectal cancer, located within 12cm of the anal verge, who haven't had chemotherapy or radiation for colorectal cancer in the last 5 years. They must be healthy enough to participate (ECOG <=2), not pregnant or nursing, and willing to use effective contraception. People with certain heart conditions, HIV on effective treatment, and those not on strong CYP3A4 inhibitors/inducers are eligible.

What is being tested?

The study tests if adding Irinotecan to standard FOLFOX chemotherapy after long-course radiation improves complete response rates and organ preservation in advanced-stage rectal cancer patients compared to using FOLFOX alone.

What are the potential side effects?

Potential side effects include nausea, vomiting, diarrhea, fatigue, hair loss from Irinotecan; nerve damage (neuropathy), allergic reactions from Oxaliplatin; mouth sores and low blood counts from both chemotherapies.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Clincal Complete Response (cCR) Rates

Secondary study objectives

Disease-free survival (DFS) rate

Incidence of adverse events (AEs)

Organ-preservation-time (OPT)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Group II (LCRT, FOLFIRINOX)Experimental Treatment10 Interventions

Patients receive long-course chemoradiation therapy on study and then receive FOLFIRINOX regimen consisting of leucovorin IV, fluorouracil IV, irinotecan IV, and oxaliplatin IV on study. Patients undergo CT scan, MRI scan, and blood specimen collection throughout the trial. Patients undergo sigmoidoscopy throughout the trial and biopsy during screening.

Group II: Group I (LCRT, FOLFOX or CAPOX)Active Control9 Interventions

Patients receive long-course chemoradiation therapy on study and then receive either: FOLFOX regimen consisting of leucovorin IV, fluorouracil IV, and oxaliplatin IV or CAPOX consisting of capecitabine PO, and oxaliplatin IV on study. Patients undergo CT scan, MRI, and biospecimen collection throughout the trial. Patients also undergo sigmoidoscopy throughout the trial and biopsy during screening.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Leucovorin calcium

2014

Completed Phase 3

~3620

Computed Tomography

2017

Completed Phase 2

~2740

Oxaliplatin

2011

Completed Phase 4

~2890

Irinotecan

2017

Completed Phase 3

~2590

Capecitabine

2013

Completed Phase 3

~3960

biopsy

2002

Completed Phase 4

~8270

Sigmoidoscopy

2007

Completed Phase 2

~140

5-fluorouracil

2005

Completed Phase 4

~8440

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for rectal cancer, such as FOLFOX (fluorouracil, leucovorin, oxaliplatin) and CAPOX (capecitabine, oxaliplatin), work through various mechanisms to inhibit tumor growth. Fluorouracil and capecitabine are antimetabolites that interfere with DNA synthesis, preventing cancer cells from dividing. Oxaliplatin is a platinum-based drug that causes DNA crosslinking, leading to cell death. Irinotecan, a topoisomerase I inhibitor, prevents DNA unwinding, which is crucial for replication and transcription. These mechanisms are vital for rectal cancer patients as they target different aspects of cancer cell proliferation, increasing the likelihood of treatment success and potentially improving outcomes.