A Study to Evaluate the Safety and Feasibility of Irinotecan, Trifluridine/Tipiracil (TAS-102), and Oxaliplatin (iTTo) for Treatment Naive Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Irinotecan
- Conditions
- Gastroesophageal Junction Adenocarcinoma
- Sponsor
- AHS Cancer Control Alberta
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Safety/Tolerability
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study will evaluate the safety and feasibility of Irinotecan, Trifluridine/Tipiracil (TAS-102) and Oxaliplatin (iTTo) for treatment naïve advanced gastric or gastroesophageal junction adenocarcinoma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be 18 years of age or older.
- •Histologically documented locally advanced or metastatic gastric or GEJ adenocarcinoma not previously treated with palliative systemic therapy.
- •Patients must be capable of providing consent to enrolment and treatment.
- •Patients with a performance status of ECOG 0-1 will be eligible for enrolment (see appendix 1).
- •Measurable disease must be present according to RECIST criteria V1.1 (see appendix ).
- •Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
- •Patients (men and women) of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
- •Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 30 days after the last dose of study drug.
- •Male patients should agree to not donate sperm during the study and for a period of at least 6 months after last dose of study drug.
- •Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
Exclusion Criteria
- •Patients who have received prior palliative chemotherapy for their advanced gastric or GEJ tumor.
- •Prior curative or palliative radiation treatment to the pelvis or radiation therapy to ≥ 25% of bone marrow stores.
- •History of bowel obstruction due to peritoneal metastases or clinically documented ascites requiring paracenteses.
- •Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment, unless at least 5 years have elapsed since last treatment and the patient is considered cured).
- •Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
- •Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.
- •Any serious medical condition within 6 months prior to study entry such as myocardial infarction, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases, uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder, serious infection, active peptic ulcer disease, or other medical condition that may be aggravated by treatment.
- •Pre-existing neuropathy ≥ grade 2 from any cause.
- •Patients with unstable metastasis to the central nervous system (CNS). A CT scan or MRI is NOT required to rule out brain metastases unless there is clinical suspicion of CNS involvement.
- •Pregnant or lactating women; women of child bearing potential must have a negative serum pregnancy test within 7 days of trial registration. Women or men of child bearing potential must use effective contraception (defined by the treating physician) which must be documented in study CRFs.
Arms & Interventions
Single Arm iTTO treatment
Patients will receive the combination of irinotecan, TAS-102, and Oxaliplatin on a 28 day cycle with the following doses; * Irinotecan 160mg/m2 IV infusion over 60-90 mins on day 1 * Oxaliplatin 100mg/m2 IV infusion over 2 hours on day 1 * TAS-102 (Trifluridine/Tipiracil) 25mg/m2 twice a day, on days 1-5 and 8-12 every 28days.
Intervention: Irinotecan
Single Arm iTTO treatment
Patients will receive the combination of irinotecan, TAS-102, and Oxaliplatin on a 28 day cycle with the following doses; * Irinotecan 160mg/m2 IV infusion over 60-90 mins on day 1 * Oxaliplatin 100mg/m2 IV infusion over 2 hours on day 1 * TAS-102 (Trifluridine/Tipiracil) 25mg/m2 twice a day, on days 1-5 and 8-12 every 28days.
Intervention: Oxaliplatin
Single Arm iTTO treatment
Patients will receive the combination of irinotecan, TAS-102, and Oxaliplatin on a 28 day cycle with the following doses; * Irinotecan 160mg/m2 IV infusion over 60-90 mins on day 1 * Oxaliplatin 100mg/m2 IV infusion over 2 hours on day 1 * TAS-102 (Trifluridine/Tipiracil) 25mg/m2 twice a day, on days 1-5 and 8-12 every 28days.
Intervention: TAS 102 (Trifluridine/Tipiracil)
Outcomes
Primary Outcomes
Safety/Tolerability
Time Frame: Through study completion, up to 2 years.
Treatment related and non-related adverse events per CTCAE v.5.0 of iTTo for the treatment of advanced gastric and GEJ cancers. Incidence of adverse events, the number of dose modifications and discontinuations due to adverse events.
The number of participants who complete at least 2 cycles of iTTo for the treatment of advanced gastric and GEJ cancers, over the total duration of study
Time Frame: 1 year after enrolment of last participant.
The number of participants who complete at least 2 cycles of iTTo for the treatment of advanced gastric and GEJ cancers, over the total duration of study.
Secondary Outcomes
- Objective Response Rate(1 year after enrollment of last participant.)
- Progression Free Survival(5 years from final study drug dose.)
- Overall Survival(5 years from final study drug dose.)