Small Bowel Adenocarcinoma
Conditions
Brief summary
The study regimen will be administered on an outpatient basis and all medications are administered intravenously (IV). Subjects will receive treatment on Day 1 and Day 15 of each 28-day cycle consisting of the following: nanoliposomal irinotecan at 50 mg/m2, followed by oxaliplatin 60 mg/m2, followed by leucovorin at 400 mg/m2 30 minutes after completion of oxaliplatin, followed by 5-FU 2400 mg/m2 60 minutes after leucovorin completion. Subjects will receive up to 6 cycles of NALIRIFOX then based on response and per physician discretion, de-escalated maintenance treatment with NALIRIFOX minus oxaliplatin may continue. Subjects will continue de-escalated maintenance treatment until progression per RECIST 1.1, intolerable toxicity or physician/subject choice to discontinue.
Interventions
Nanoliposomal Irinotecan 50 mg/m2 will be administered over 90 minutes (± 10 minutes) IV. All subjects must be pre-medicated prior to nanoliposomal irinotecan infusion with standard doses of dexamethasone and a 5-HT3 antagonist, or equivalent other anti-emetics (according to standard institutional practices).
DRUGOxaliplatin
Oxaliplatin 60 mg/m2 will be administered over 120 minutes (± 10 minutes) IV. Institutional standards may be used for all aspects of oxaliplatin administration including premedication administration.
DRUG5 fluorouracil
5-FU will be administered as a continuous infusion over 46 hours. Subjects will go home with an infusion pump and return to clinic at the end of infusion for removal of the pump or, if possible, the pump may be removed at the subject's home (except on Cycle 1 Day 3).
DRUGLeucovorin
Leucovorin 400 mg/m2 will be administered over 30 minutes IV.
Sponsors
Tiago Biachi de Castria
Ipsen
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will receive treatment on Day 1 and Day 15 of each 28-day cycle consisting of the following: nanoliposomal irinotecan at 50 mg/m2, followed by oxaliplatin 60 mg/m2, followed by leucovorin at 400 mg/m2 30 minutes after completion of oxaliplatin, followed by 5-FU 2400 mg/m2 60 minutes after leucovorin completion. Patients will receive up to 6 cycles of NALIRIFOX then based on response and per physician discretion, de-escalated maintenance treatment with NALIRIFOX minus oxaliplatin may continue. Subjects will continue de-escalated maintenance treatment until progression per RECIST 1.1, intolerable toxicity or physician/subject choice to discontinue.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the ICF prior to participation in any study-related activities. Also, as determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. 2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of ≤ 1 within 28 days prior to registration. 4. Histological or cytologically confirmed small bowel adenocarcinoma per AJCC staging manual, 8th edition that has not been previously treated in the metastatic setting. Subjects with only localized disease or disease which will likely become resectable after chemotherapy (per investigator discretion) are NOT eligible. NOTE: Subjects may have received one cycle of FOLFOX without biologic therapy prior to screening for this trial. 5. Mismatch repair proficient (MMRp) and/or microsatellite stable (MSS) disease per institutional standard of care testing. NOTE: Testing should be performed prior to receipt of one cycle of FOLFOX. 6. Subject has one or more metastatic lesion(s) measurable by CT scan (or MRI, if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria. Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable. 7. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration. * Platelets (Plt) ≥ 100,000 cells/mm3 * Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3; without the use of hemopoietic growth factors * Hemoglobin (Hgb) ≥ 9 g/dL * Calculated creatinine clearance ≥ 30 mL/min; Cockcroft-Gault formula for actual body weight should be used for calculation. For subjects with a body mass index (BMI) \> 30 kg/m2, adjusted body weight should be used instead * Total bilirubin ≤ 1.5 × ULN * Aspartate aminotransferase (AST) ≤ 2 × ULN; \< 5× with liver metastases * Alanine aminotransferase (ALT) ≤ 2 × ULN; \< 5× with liver metastases * Albumin ≥ 2.5 gm/dL * PT/INR and aPTT ≤ 1.5 x ULN; subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor-investigator. * Urinalysis: Urinalysis results without clinically significant abnormalities, per the investigator's assessment 8. Subjects treated in the adjuvant setting who completed treatment \> 6 months prior to registration and do not have residual toxicities \> Grade 1 are eligible. 9. Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia's formula (QTcF) ≤450 msec and no known arrhythmias) and per the investigator's assessment. 10. Females of childbearing potential must have a negative urine or serum pregnancy test within ≤ 7 days prior to registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 11. Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. 12. Subjects with known human immunodeficiency virus (HIV) are eligible if they meet all the following criteria: * CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications; * Probable long-term survival with HIV if cancer were not present; * Stable on a highly active antiretroviral therapy (HAART) regimen for ≥ 4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study; * HIV is not multi-drug resistant; * Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication. NOTE: Testing for HIV is not required at screening unless mandated by local policy. If a subject is known to be HIV positive, testing is required as described above to meet eligibility requirements. 13. Subjects with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. For subjects with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. NOTE: Testing for HBV and HCV is not required at screening unless mandated by local policy. If a subject is known to have an HBV and/or HCV infection, testing is required as described above to meet eligibility requirements.
Exclusion criteria
1. Adenocarcinoma originating in the ampulla or appendix. NOTE: Duodenal tumors that involve the ampulla but originate in the duodenum are eligible. In addition, ampullary cancers that demonstrate an intestinal phenotype based on H\&E and/or IHC (excluding biliary phenotype) are eligible. 2. Neuroendocrine or any other histology different than adenocarcinoma. 3. Prior treatment with irinotecan. 4. Prior treatment of small bowel adenocarcinoma (SBA) in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy: * Palliative radiotherapy is permitted but lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable. * Placement of biliary stent/tube is permitted. * Palliative surgery (for example to treat obstruction) 5. Known history of central nervous system (CNS) metastases. NOTE: Subjects on a stable or decreasing dose of steroids that are deemed clinically stable as per the investigator's assessment may be eligible, providing they meet all inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 3 years | ORR is defined as the proportion of subjects with a confirmed complete or partial response to treatment according to RECIST 1.1, by local assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 3 years | OS is defined as the time from initiation of study regimen to date of death due to any cause. |
| Time to Progression (TTP) | 3 years | TTP is defined as the time from initiation of study regimen to date of disease progression by RECIST 1.1. |
| Duration of Response (DOR) | 3 years | DOR is defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD (per RECIST 1.1) or ro death due to any cause, whichever comes first. |
| Number of Participants with Adverse Events | 3 years | Adverse events will be assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5. |
Countries
United States
Contacts
CONTACTTiago Biachi de Castria, MD, PhD
CONTACTLeaEtta Hyer
PRINCIPAL_INVESTIGATORTiago Biachi de Castria, MD, PhD
Moffitt Cancer Center
Outcome results
None listed