Dataset Information

Cimetidine for Reducing Oxaliplatin Neurotoxicity (CITRON)

ABSTRACT: Interventions: Subjects will be randomly allocated to blinded treatment with cimetidine during cycle one of oxaliplatin treatment then crossover to placebo treatment in cycle two, or will receive the same blinded treatments in the opposite sequence. Cimetidine or placebo capsules will be given as a single oral dose 0.5 hours prior to commencement of the oxaliplatin infusion. In the dose-escalation phase of the trial, the dose of cimetidine will be increased sequentially in cohorts of three patients using a traditional 3+3+3 rule-based oncology phase I clinical trial design. The dose escalation phase of the trial will explore cimetidine treatment given concurrently with oxaliplatin at six dose-levels (200, 400, 800, 1200, 1600 and 2000 mg). Following treatment of the first cohort of three patients at a given dose-level, three main possibilities exist: 1) if all three patients have DLT, then that dose-level will be declared the MTD and the next cohort of three patients will be treated at the next lowest dose-level; 2) if none of three patients have DLT, then the next cohort of three patients will be treated with the next highest dose level, and; 3) if one or two of three patients had DLT, then the next cohort of three patients will be treated at the same dose-level to expand that dose level. Dose escalation may stop when one or more of the following has occurred: 1) the maximally tolerated dose of cimetidine is reached; 2) cimetidine was found to significantly alter the pharmacokinetics of oxaliplatin, or; 3) the recommended dose for cohort expansion of cimetidine has been reached. After identifying a cimetidine dose recommended for cohort expansion, 30 patients will be recruited to receive a fixed dose of cimetidine using the crossover design to generate clinical p Primary outcome(s): Plasma pharmacokinetics of intact oxaliplatin defined by plasma concentration at steady-state (Css) and area under the plasma concentration-versus-time curve (AUC) of intact oxaliplatin [Single plasma sample will be collected and processed at the end of infusion on Day 1 of Cycles 1 and 2 for the main study. For the optional sub-study, 16 plasma samples will be collected at pre-infusion, at 20, 40, 60 and 90 minutes after the start of the oxaliplatin infusion, at the end of the infusion and 5, 10, 20, 30, 60, 120, 180, 300 minutes, 24 and 72 hours, thereafter.] Study Design: Purpose: Treatment; Allocation: Randomised controlled trial

DISEASE(S): Cancer-biliary Tree (gall Bladder And Bile Duct),Cancer-bowel-anal,Cancer-bowel-small Bowel (duodenum And Ileum),Cancer-bladder,Cancer-pancreatic,Cancer-stomach,Gastrointestinal Cancer,Colorectal Cancer,Cancer-bowel-back Passage (rectum) Or Large Bowel (colon),Cancer-oesophageal (gullet),Cancer-liver

PROVIDER: 2468642 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Interventions: Irinotecan (180mg/m2), and Panitumumab (6mg/Kg), will be administered intravenously (IV) on Day 1 of every 14 day cycle. Trifluridine/tipiracil will be administered orally (PO) twice a day (BD) on Days 1-5 of every 14 day cycle. Trifluridine/tipiracil will be supplied as 15 mg (comprising 15 mg trifluridine/6.14 mg tipiracil) and 20 mg (comprising 20 mg trifluridine/8.19mg tipiracil) immediate-release film-coated tablets and the number of tablets needed to achieve the assigned dose will be determined according to the patient’s body surface area. Dosing of trifluridine/tipiracil in the dose escalation phase (phase Ib) will be as follows: Dose LevelTrifluridine/tipiracil 1 (starting dose)25 mg/m2 orally, BD 2 30 mg/m2 orally, BD 3 35 mg/m2 orally, BD The dose escalation phase (phase Ib) will recruit participants who have received and failed one prior chemotherapy regimen for metastatic colorectal cancer (mCRC). It is anticipated that this phase of the study will take 6 months to complete. The maximum (MTD) will be assessed during the dose escalation phase, where participants will be enrolled in cohorts. Each cohort will consist of a minimum of 3 newly enrolled evaluable patients. If there is no dose-limiting toxicities (DLT) in the first 3 patients within a cohort, a new cohort at the next dose level will commence. If safety data show one patient in a cohort experiencing a DLT, then the cohort will be increased to a maximum of six evaluable patients. If no more than one of the six patients experiences a DLT, then the next dose level may be evaluated. If two or more patients entered in any cohort experience a DLT, then the MTD has been exceeded, and the previous dose level will be considered the MTD. If no dose level has 2 or more DLT`s, then dose level 3 will be considered the MTD. A minimum of 6 evaluable patients will be treated at the dose level before the dose can be declared as the MTD and enrolment into the phase II component can begin. Cohorts may also be expanded at any dose level to further assess safety parameters as required. If a dose level is opened and patients in the previous cohort subsequently develop unexpected toxicities the cohort will be closed and the previous cohort will be re-assessed with further patients enrolled into the previous cohort as required. The maximum tolerated dose (MTD) of tipiracil/trifluridine will be the dose level administered in the expansion phase (phase II). The expansion phase (phase II) will recruit participants that have received no prior treatment for mCRC, and is anticipated to take up to 18 months to complete. Treatment will continue until disease progression or withdrawal criteria are met.

Project description:Interventions: Combination treatment using cetuximab, cobimetinib and palbociclib. This is a two part open label study using escalating doses of these drugs. Phase 1 will enroll 3-6 patients in one of 6 Cohorts, for dose escalation. The initial dose escalation will start at cetuximab 150mg/m2 intravenously (IV) + cobimetinib 20 mg orally once daily (po qd) + palbociclib 50mg orally once daily (po qd), for Cohort 1. Cohort 2 = cetuximab 150mg/m2 IV + cobimetinib 20 mg po qd + palbociclib 75mg po qd. Cohort 3 = cetuximab 150mg/m2 IV + cobimetinib 40 mg po qd + palbociclib 75mg po qd. Cohort 4 = cetuximab 150mg/m2 IV + cobimetinib 60 mg po qd + palbociclib 75mg po qd. Cohort 5 = cetuximab 200mg/m2 IV + cobimetinib 60 mg po qd + palbociclib 75mg po qd. Cohort 6 = cetuximab 250mg/m2 IV + cobimetinib 60 mg po qd + palbociclib 100mg po qd. Cetuximab will be administered weekly via intravenous infusion. Cobimetinib will be taken orally once daily for the first 21 consecutive days in a 28 day treatment cycle. Cobimetinib will be taken in tablet form. Palbociclib will be taken orally once daily for first 21 consecutive days in a 28 day treatment cycle. Palbociclib will be taken in capsule form. Neither of these two drugs will be given in the last 7 days of this 28 day cycle. Cohorts of 3 patients will be enrolled at each dose level (with the option of up to six patients for each cohort if necessary) to assess toxicity. Each patient will participate in only one cohort to determine dose limiting toxicities of the combination. Patients at each dose level will be treated and observed through the end of the first cycle before treatment of subjects at the next higher dose level can begin. Cohorts 1 to 6 will randomly assign consecutive patien Primary outcome(s): Phase 1: Determination of Dose Limiting Toxicity (DLT). A DLT will be defined using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v 5.0 [Phase 1 DLTs will be assessed during the first cycle of treatment (28 days) and are events that are considered possiby related to the study drug combination for each cohort. After the treatment of each cohort, data will be reviewed to assess patient status and study drug related toxicities from the current cohort before deciding the escalation plan and dose level for the next cohort. ];Phase 2: Determination of Objective Response Rate as determined by MRI scanning with RECIST criteria reporting[Phase 2: patients will be reviewed for objective response rate after at least 2 treatment cycles] Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Other;Type of endpoint: Safety

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Cimetidine for Reducing Oxaliplatin Neurotoxicity (CITRON)

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