Clinical Trial TitleAn open-label, randomised, multicentre, phase III study of irinotecan liposome injection, oxaliplatin, 5-fluorouracil/leucovorin versus nab-paclitaxel plus gemcitabine in subjects who have not previously received chemotherapy for metastatic adenocarcinoma
National Clinical Trial Number:NCT04083235
Clinical Trial Protocol Description:
The purpose of this study:
To look at how safe and helpful the study drug, irinotecan liposome injection, is when given together with the approved cancer drugs 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared
to the approved cancer drugs nab-paclitaxel plus gemcitabine.
To determine how helpful the treatments are, your tumor will be measured by scans (CT or MRI) and you will be followed for any further treatments you receive for your cancer and followed for your health status.
Clinical Trial Eligibility Criteria:
In order to participate you must meet the following criteria:
- Have been informed about the nature of the study, and has agreed to participate in the study, and signed the informed consent form (ICF) prior to participation in any study-related activities.
- Are male or non-pregnant and non-lactating female and ≥18 years of age:
- Females of child-bearing potential (i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Female subjects of reproductive potential must agree to use a highly effective method of birth control, during the study and for 6 months following the last dose of study medication (see also Appendix 4 and Section 4.3.3).
- Male subjects must agree to use condoms during the study and for 6 months following the last dose of study medication.
- Have histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
- Have an Iinitial diagnosis of metastatic disease (as per American Joint Committee on Cancer 8th Edition [AJCC 2017]) must have occurred ≤6 weeks prior to screening.
- Have one or more metastatic tumours measurable by computed tomography (CT) scan (or magnetic resonance imaging (MRI), if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and within 7 days prior to randomisation.
- Have adequate biological parameters as demonstrated by the following blood counts:
- Absolute neutrophil count (ANC) ≥2000/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation
- Platelet count ≥100,000/mm3
- Haemoglobin (Hgb) ≥9 g/dL obtained ≤14 days prior to randomisation.
- Have adequate hepatic function as evidenced by:
- Serum total bilirubin ≤1.5x upper limit of normal (ULN) (biliary drainage is allowed for biliary obstruction), and
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN (≤5x ULN is acceptable if liver metastases are present).
- Have adequate renal function with a creatinine clearance (CLCR) of >30 mL/min. Actual body weight should be used for calculating CLCR using the Cockcroft-Gault Equation: CLCR (mL/min) = ((140–Age [years]) * (Weight [kg]/(Serum Creatinine [mg/dL]*72). Multiply the result by 0.85 if the subject is female. For subjects with a body mass index (BMI) >30 kg/m2, adjusted body weight should be used instead.
- Have an 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.
- Have adequate coagulation studies (obtained ≤14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (≤1.5 x ULN). (Subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor).
- Have no clinically significant abnormalities in urinalysis results (obtained within the last 7 days prior to randomisation), per the investigator’s assessment.
- Subjects infected with 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.
You will be excluded from the study if any of the following criteria apply to you:
- Have any other medical or social condition deemed by the investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
- Are unwilling or unable to comply with study procedures and/or study visits.
- Have had prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy:
- Palliative radiotherapy is permitted.
- Placement of biliary stent/tube is permitted.
- Have had prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present.
- Have only localised advanced disease.
- Have documented serum albumin <3 g/dL within 7 days prior to randomisation.
- Have a 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).
- Have clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhoea >Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease or partial bowel obstruction.
- Have a 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 tumour-directed treatment are eligible.
- Have known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
- Have known hypersensitivity to any of the components of nab-paclitaxel or gemcitabine.
- Have concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including:
- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening
- High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to screening
- New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
- Known historical or active infection with hepatitis B, or active infection with hepatitis C (note that subjects with hepatitis C who have been clinically cured, defined as persistent absence of hepatitis C ribonucleic acid (RNA) detected by polymerase chain reaction (PCR) test in serum 12 weeks after completing antiviral treatment, are eligible for this study)
- Have active infection or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumour fever may be enroled), which in the investigator’s opinion might compromise the subject’s participation in the study or affect the study outcome.
- Have had major surgery, other than diagnostic surgery, within 4 weeks prior to randomisation.
- Have use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 (please refer to Appendix 1). 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 randomisation
- They are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to randomisation.
- There is presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the investigator brochure (IB) for irinotecan liposome injection, or in the prescribing information for 5-FU, LV or oxaliplatin.
- There is presence of any contraindications outlined in the Contraindications or Special Warnings and Precautions sections of the product prescribing information for nab-paclitaxel or gemcitabine.
- Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
- 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).
- History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
- History of peripheral artery disease (e.g. claudication, Leo Buerger's disease).
- Subjects who have received a live vaccine within 4 weeks prior to randomisation.
- Known low or absent dihydropyrimidine dehydrogenase (DPD) activity. Where required by local regulations, testing for DPD deficiency must be performed using a validated method which is recommended by local health authorities.
This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.