Irinotecan + FOLFOX Chemotherapy for Rectal Cancer
(JANUS Trial)
Recruiting in Palo Alto (17 mi)
+683 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alliance for Clinical Trials in Oncology
Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers
Disqualifiers: Pregnancy, Upper rectal tumors, others
No Placebo Group
Prior Safety Data
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers (types of drugs that affect how your body processes other medications) at least 14 days before starting the study treatment.
What data supports the effectiveness of the drug combination Irinotecan and Oxaliplatin for rectal cancer?
Research shows that the combination of Irinotecan and Oxaliplatin is effective in treating advanced colorectal cancer, which is similar to rectal cancer. Studies have found that these drugs work well together and can be used as a first-line treatment, meaning they are often the first choice for treating this type of cancer.
12345Is the combination of Irinotecan and Oxaliplatin safe for humans?
The combination of Irinotecan and Oxaliplatin, used in chemotherapy for colorectal cancer, has been associated with various side effects such as myelosuppression (reduced bone marrow activity), diarrhea, nausea, and neurotoxicity (nerve damage). While these drugs can be effective, they may cause significant toxicity, and managing these side effects is important for patient safety.
678910How is the drug Irinotecan + FOLFOX different for rectal cancer treatment?
The combination of Irinotecan and FOLFOX, which includes oxaliplatin, is unique because it combines multiple chemotherapy agents that work together to improve outcomes in colorectal cancer, especially when other treatments have failed. This regimen is notable for its synergistic effects and non-overlapping side effects, potentially offering better response rates compared to standard treatments.
111121314Eligibility Criteria
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.Inclusion Criteria
I can take care of myself but might not be able to do heavy physical work.
Platelet count >= 100,000/mm
My kidney function, measured by creatinine levels or clearance, is within the normal range.
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Radiation
Participants receive long-course chemoradiation therapy
5-6 weeks
Weekly visits (in-person)
Chemotherapy
Participants receive either FOLFOX or CAPOX regimen in Group I, or FOLFIRINOX regimen in Group II
8-12 weeks
Bi-weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Regular visits (in-person and virtual)
Participant Groups
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.
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.
Oxaliplatin is already approved in European Union, United States, Canada, Japan, Switzerland, China for the following indications:
🇪🇺 Approved in European Union as Eloxatin for:
- Colorectal cancer
🇺🇸 Approved in United States as Eloxatin for:
- Colorectal cancer
🇨🇦 Approved in Canada as Eloxatin for:
- Colorectal cancer
🇯🇵 Approved in Japan as Eloxatin for:
- Colorectal cancer
🇨🇭 Approved in Switzerland as Eloxatin for:
- Colorectal cancer
🇨🇳 Approved in China as Ai Heng for:
- Colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Missouri Baptist Medical CenterSaint Louis, MO
Mount Sinai HospitalNew York, NY
Memorial Hospital of CarbondaleCarbondale, IL
Illinois CancerCare-CarthageCarthage, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Alliance for Clinical Trials in OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer. [2018]To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines.
Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis. [2018]To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer.
A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer. [2020]To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer.
Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer. [2018]Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs act synergistically, a randomized phase II study was initiated to investigate the therapeutic potential and tolerance of this combination in the front-line setting.
[The validity of full administration of 5-fluorouracil, irinotecan, and oxaliplatin to unresectable or recurrent colorectal cancer]. [2018]This retrospective study was performed to evaluate a survival benefit of the full administration of 5-fluorouracil (5-FU), irinotecan (CPT-11), and oxaliplatin (L-OHP) to patients with unresectable or recurrent colorectal cancer.
Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer. [2018]The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.
Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer. [2013]Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741.
Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer. [2018]Oxaliplatin or irinotecan is usually administered jointly with fluoropyrimidines in colorectal cancer patients treated with chemotherapy. Both drugs have different toxicity patterns. Biomarkers for predicting high-risk severe adverse reactions can help select the best treatment.
Oxaliplatin plus irinotecan and leucovorin-modulated 5-fluorouracil triplet regimen every other week: a dose-finding study in patients with advanced gastrointestinal malignancies. [2020]Oxaliplatin (OXA) and irinotecan (IRI) are active drugs in first-line as well as second-line treatment of advanced colorectal cancer patients, their toxicity profiles are not overlapping, and both drugs have shown synergism with folinic acid-modulated 5-fluorouracil (5-FU). We planned this phase I study to define the dose-limiting toxicities (DLTs), the maximum tolerated doses (MTDs), and the recommended doses (RDs) for a triplet regimen including OXA plus IRI on day 1, and 6S-folinic acid (LFA) plus 5-FU on day 2, every 2 weeks.
A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. [2018]The simultaneous administration of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin (FOLFOXIRI) has been compared with standard 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) in randomized trials in metastatic colorectal cancer patients. A superior efficacy of FOLFOXIRI has been reported by some authors, but others have failed to show any differences and do not recommend its use because of greater cost and toxicity. We performed a systematic review of the literature to analyse efficacy and toxicity of FOLFOXIRI.
Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis in advanced colorectal cancer patients. [2019]This phase I-II trial was designed to assess the effect of irinotecan on oxaliplatin pharmacokinetics and to determine the MDT of both drugs when administered in combination. Treatment was repeated every 2 weeks. Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs. Thirty-four patients with advanced colorectal cancer were enrolled; 28 of them (82%) had liver involvement. The main toxicities were neutropenia and delayed diarrhea; 5 patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients, respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No pharmacokinetic interactions between irinotecan and oxaliplatin were detected. The recommended dose for future phase II trials is oxaliplatin 85 mg/m and irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent secondary hepatectomy with curative intent, and two of them are long-term disease-free survivors. It would appear that the dose and schedule defined by this trial could be proposed as front-line therapy for advanced colorectal carcinoma to establish rapid disease control and to permit patients to proceed to surgery.
Phase II trial of oxaliplatin/irinotecan/5-fluorouracil/leucovorin for metastatic colorectal cancer. [2018]Individually, oxaliplatin and irinotecan have substantial activity in metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin. A combination regimen using all 4 agents could potentially increase response rates in CRC.
FOLFOXIRI plus biologics in advanced colorectal cancer. [2020]The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes.
Efficacy of treatment with irinotecan and oxaliplatin combination in FU-resistant metastatic colorectal cancer patients. [2018]As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer.