Clinical Trial 23375

• Overview

  Study Title:

  Phase II Study of NALIRIFOX (Nanoliposomal Irinotecan + Oxaliplatin with Fluorouracil and Folinic Acid) in Advanced Unresectable Small Bowel Tumors

  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.

  Objective:

  Primary Objective Determine the activity of NALIRIFOX as measured by objective response rate (ORR) in patients with unresectable or metastatic small bowel adenocarcinoma. Secondary Objectives * Evaluate overall survival (OS) * Evaluate time to progression (TTP) * Evaluate Duration of response (DOR) * Assess the safety and tolerability of NALIRIFOX in this patient population.

• Treatments

  Therapies:

  Chemotherapy (NOS)

  Medications:

  5-fluorouracil (); Nanoliposomal Irinotecan (); Oxaliplatin (); eloxatin (Oxaliplatin); leucovorin ()

• Inclusion Criteria

  Inclusion Criteria:
  • 18 years of age or older
  • ECOG Performance Status of 1 or less within 28 days prior to registration and within 7 days prior to start of study regimen.
  • Histological or cytologically confirmed small bowel adenocarcinoma per AJCC, 9th edition that has not been previously treated in the metastatic setting. Participants treated in the adjuvant setting who completed treated over 6 months and do not have residual toxicities over Grade 1 are eligible. NOTE: Participants with only localized disease or disease which will likely become resectable after chemotherapy (per investigator discretion) are NOT eligible.
  • Mismatch repair proficient (MMRp) and/or microsatellite stable (MSS) disease per institutional standard of care testing.
  • Participant has one or more metastatic lesions measurable by CT scan (or MRI, if the participant 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.
  • Demonstrate adequate organ function as defined in protocol. All screening labs to be obtained within 28 days prior to registration and repeated within 7 days prior of C1D1.
  • 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.
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days or less 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.
  • 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.
  • Participants infected with human immunodeficiency virus (HIV) are eligible if they meet all the criteria outlined in protocol. NOTE: Testing is not required at screening unless mandated by local policy.
  • Participants with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. NOTE: Testing is not required at screening unless mandated by local policy.
  • Other criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • Adenocarcinoma originating in the ampulla or appendix (duodenal tumors that involve the ampulla but originate in the duodenum are eligible).
  • Neuroendocrine or any other histology different than adenocarcinoma.
  • Prior treatment with irinotecan.
  • Prior treatment of 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.
  • Known history of central nervous system (CNS) metastases. (subjects on a stable or decreasing dose of steroids and deemed clinically stable as per the investigator's assessment are eligible).
  • Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea > Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction.
  • Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
  • History of any second malignancy in the last 2 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years prior to screening. Subjects who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible.
  • Known hypersensitivity to any of the components of nanoliposomal irinotecan, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
  • Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including: (a) Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening (b) High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to screening (c) New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
  • Active infection or an unexplained fever greater than 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled), which in the investigator's opinion might compromise the subject's participation in the study or affect the study outcome.
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to consent.
  • Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are ineligible if: they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8 and UGT1A1 at least 1 week prior to consent; they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to consent.
  • There is presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the IB for nanoliposomal irinotecan, or in the prescribing information for 5-FU, LV or oxaliplatin.
  • Subjects who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
  • History of systemic connective tissue disorders (e.g. lupus, scleroderma, arteritis nodosa).
  • Subjects who have received a live vaccine within 4 weeks prior to consent.
  • Other criteria apply

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