NCT05610163: JANUS

Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage Rectal Cancers to Improve the Rate of Complete Response and Long-Term Rates of Organ Preservation

Active, enrolled Phase 2 Last updated 8 September 2025

What this trial tests

Phase 2 trial testing Capecitabine in Locally Advanced Rectal Carcinoma in 783 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

8 December 2022

Primary endpoint
30 September 2026

30 September 2033

Quick facts

Lead sponsor	Alliance for Clinical Trials in Oncology
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	783
Start date	8 December 2022
Primary completion	30 September 2026
Estimated completion	30 September 2033
Sites	685 locations across Puerto Rico, United States

Drugs / interventions tested

• Capecitabine (capecitabine) — full drug profile →
• 5-fluorouracil
• Leucovorin calcium
• Irinotecan (irinotecan) — full drug profile →
• Oxaliplatin (Oxaliplatin) — full drug profile →
• Long Course Chemoradiotherapy
• Computed Tomography
• Magnetic Resonance Imaging
• Sigmoidoscopy
• biopsy

Conditions studied

• Locally Advanced Rectal Carcinoma — all drugs for Locally Advanced Rectal Carcinoma →
• Stage II Rectal Cancer AJCC v8 — all drugs for Stage II Rectal Cancer AJCC v8 →
• Stage III Rectal Cancer AJCC v8 — all drugs for Stage III Rectal Cancer AJCC v8 →

Sponsor

Alliance for Clinical Trials in Oncology

Who can join

18 and older, any sex, with Locally Advanced Rectal Carcinoma or Stage II Rectal Cancer AJCC v8. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This phase II trial compares the effect of irinotecan versus oxaliplatin after long-course chemoradiation in patients with stage II-III rectal cancer. Combination chemotherapy drugs, such as FOLFIRINOX (fluorouracil, irinotecan, leucovorin, and oxaliplatin), FOLFOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan ), and CAPOX (capecitabin and oxaliplatin) 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. FOLFOX or CAPOX are used after chemoradiation as usual treatment for rectal cancer. Giving FOLFIRINOX after chemoradiation may increase the response rate and lead to higher rates of clinical complete response (with a chance of avoiding surgery) compared to FOLFOX or CAPOX after chemoradiation in patients with locally advanced rectal cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Future direction of total neoadjuvant therapy for locally advanced rectal cancer.
   Kagawa Y, Smith JJ, Fokas E, Watanabe J, et al · · 2024 · cited 63× · PMID 38485756 · DOI 10.1038/s41575-024-00900-9
2. Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.
   Alvarez JA, Shi Q, Dasari A, Garcia-Aguilar J, et al · · 2024 · cited 28× · PMID 39060961 · DOI 10.1186/s12885-024-12529-7
3. A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.
   Romesser PB, Capdevila J, Garcia-Carbonero R, Philip T, et al · · 2024 · cited 21× · PMID 38051750 · DOI 10.1158/1078-0432.ccr-23-1129
4. Adoption of Total Neoadjuvant Therapy in the Treatment of Locally Advanced Rectal Cancer.
   Conces ML, Mahipal A. · · 2024 · cited 6× · PMID 38248109 · DOI 10.3390/curroncol31010024
5. Landscape of Biomarkers and Pathologic Response in Rectal Cancer: Where We Stand?
   Ocanto A, Teja M, Amorelli F, Couñago F, et al · · 2024 · cited 5× · PMID 39682232 · DOI 10.3390/cancers16234047
6. Neoadjuvant Treatment for Locally Advanced Rectal Cancer: Current Status and Future Directions.
   Iwamoto M, Ueda K, Kawamura J. · · 2025 · cited 4× · PMID 40805234 · DOI 10.3390/cancers17152540
7. Mastering rectal cancer MRI: From foundational concepts to optimal staging.
   Modena Heming CA, Alvarez JA, Miranda J, Cardoso D, et al · · 2025 · cited 4× · PMID 39864243 · DOI 10.1016/j.ejrad.2025.111937
8. Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer.
   Sullo FG, Passardi A, Gallio C, Molinari C, et al · · 2024 · cited 4× · PMID 38731090 · DOI 10.3390/jcm13092562