Pilot study of SIR-Spheres plus systemic chemotherapy with irinotecan alone in patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Cancer-bowel-back Passage (rectum) Or Large Bowel (colon)
PROVIDER: 2452615 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: The study is a multi-centre phase I/II dose-escalation study that aims to assess the safety and efficacy of a single implantation of SIR-Spheres when used in combination with systemic chemotherapy with FOLFOX4. Toxicity will be assessed after 3 cycles of treatment, at which stage the oxaliplatin will be escalated to full dose and the patients will go on receive a maximum of 12 cycles of chemotherapy. (The duration of the treatment cycles varies as it is based on the doctor’s discretion. Ideally the treatment cycles would be 1 week of treatment and then 1 week of rest.)
Primary outcome(s): Toxicity[Assessed using standard UICC criteria which will be assessed after patients have completed 12 cycles of chemotherapy.]
Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy
| 2452613 | ecrin-mdr-crc
Project description:Purpose: Novel antibody-drug conjugates (ADCs) have shown potent antitumor activity across multiple cancer types. Here, we aimed to identify potential determinants of response to patritumab deruxtecan (HER3-DXd), a HER3-directed ADC linked to a potent topoisomerase I inhibitor (TOP1i) payload, in breast cancer (BC) patient-derived xenograft (PDX) models. Experimental Design: The antitumor activity of HER3-DXd was assessed in 31 BC PDXs and classified according to tumor growth inhibition and duration of response. We analyzed the sensitivity to HER3-DXd according to the molecular characteristics of the PDX models, the sensitivity to the TOP1i irinotecan, and prior patient treatments. The biological effects following treatment with HER3- DXd were assessed and associated to treatment response. Results: Fourteen out of 31 (45%) PDXs exhibited a profound and sustained response to HER3-DXd. Basal-like PAM50 intrinsic subtype was associated with long-term response, across HER3/ERBB3 expression levels. We also observed a positive association between HER3-DXd and irinotecan sensitivity in the PDXs, as well as short-lasting antitumor response in models derived from patients with prior repeated exposure to chemotherapy. HER3-DXd showed sustained activity in BRCA1/BRCA2-mutated PARPi-resistant PDX models. Long-term responders exhibited persistent DNA damage and lacked early transcriptional activation of the G2/M cell cycle checkpoint to allow for DNA repair and R-loop resolution, in parallel resulting in immune pathways activation. Conclusions: HER3-DXd exhibited potent antitumor activity in breast cancer PDX models, including those with BRCA1/BRCA2 alterations and PARPi resistance. Notably, characteristics linked to long-term response were primarily associated with the TOP1i payload activity.
2025-11-28 | GSE307574 | GEO
Project description:Purpose: Novel antibody-drug conjugates (ADCs) have shown potent antitumor activity across multiple cancer types. Here, we aimed to identify potential determinants of response to patritumab deruxtecan (HER3-DXd), a HER3-directed ADC linked to a potent topoisomerase I inhibitor (TOP1i) payload, in breast cancer (BC) patient-derived xenograft (PDX) models. Experimental Design: The antitumor activity of HER3-DXd was assessed in 31 BC PDXs and classified according to tumor growth inhibition and duration of response. We analyzed the sensitivity to HER3-DXd according to the molecular characteristics of the PDX models, the sensitivity to the TOP1i irinotecan, and prior patient treatments. The biological effects following treatment with HER3-DXd were assessed and associated to treatment response. Results: Fourteen out of 31 (45%) PDXs exhibited a profound and sustained response to HER3-DXd. Basal-like PAM50 intrinsic subtype was associated with long-term response, across HER3/ERBB3 expression levels. We also observed a positive association between HER3-DXd and irinotecan sensitivity in the PDXs, as well as short-lasting antitumor response in models derived from patients with prior repeated exposure to chemotherapy. HER3-DXd showed sustained activity in BRCA1/BRCA2-mutated PARPi-resistant PDX models. Long-term responders exhibited persistent DNA damage and lacked early transcriptional activation of the G2/M cell cycle checkpoint to allow for DNA repair and R-loop resolution, in parallel resulting in immune pathways activation. Conclusions: HER3-DXd exhibited potent antitumor activity in breast cancer PDX models, including those with BRCA1/BRCA2 alterations and PARPi resistance. Notably, characteristics linked to long-term response were primarily associated with the TOP1i payload activity.
2025-11-28 | GSE310422 | GEO
Project description:Chronotherapy demands that patients are treated at a particular time of the day in order to maximize treatment effects and minimize side effects. Chronotherapy can be personalized by taking into account the patient's circadian rhythm as measured by a repetitive sampling of gene expression over the day. As a proof of concept, the submitted model links circadian gene expression to the diurnal toxicity profile of the cancer drug irinotecan. The model is based on MODEL2109140001; it implements a transcription-translation network model of the core clock and additional genes associated with irinotecan metabolism and links this to a model of the pharmacokinetics and -dynamics (PK-PD) of irinotecan. The submitted model refines network connections of the gene regulatory network and adds a treatment-induced increase in UGT1A1 and a transient increase in the apoptosis rate in response to treatment for the PK-PD part.
2023-06-27 | MODEL2305270001 | BioModels
Project description:The standard treatment for canine lymphoma (cL) is the CHOP chemotherapy protocol. Most cL patients treated with CHOP initially achieve remission but the duration varies and the majority of dogs eventually relapse with a multidrug resistant phenotype. This study assesses changes in gene expression occurring in cL tumor cell populations over the course of CHOP treatment. We measured gene expression using RNA-Seq on 15 cL patient samples taken prior to treatment and again 6 weeks into treatment.
2021-07-14 | GSE179920 | GEO
Project description:Interventions: CPT-11+ Folinic Acid+ 5FU weekly for 6 weeks on days 1,8,15,22,29 and 36 (followed by 2 weeks rest for a total cycle duration of 8 weeks) at the following doses:
CPT-11: 80 mg/m2 in 250 ml normal saline intravenous injection (IV) over 90 minutes
Folinic acid: 200 mg/m2 in 500 ml normal saline IV over 2 hours
5FU: 450 mg/m2 IV bolus.
This 8-week cycle will be administered in an identical manner again (i.e. total 16 weeks).
Then, it will be followed by Oxaliplatin+ Folinic Acid+ 5FU weekly for 6 weeks on days 1,8,15,22,29 and 36 (followed by 2 weeks rest for a total cycle duration of 8 weeks) at the following doses:
Oxaliplatin: 45 mg/m2 IV over a 90 min infusion
Folinic acid: 200 mg/m2 in 500 ml normal saline IV over 2 hours
5FU: 450 mg/m2 IV bolus
This 8-week cycle will be administered in an identical manner again (i.e. total 16 weeks).
The overall duration of the intervention will be 32 weeks in total (4 cycles).
Primary outcome(s): Objective Response Rate (ORR).
The ORR will be assessed by imaging methods including computed tomography (CT) scan, bone scan, X-ray etc.[At 32 months from study initiation]
Study Design: Purpose: Treatment; Allocation: Randomised controlled trial
| 2454913 | ecrin-mdr-crc
Project description:The goal of the endurance exercise training study in young adult rats was to perform exercise training studies in young adult (6-month-old) F344 rats, and from these rats collect multiple tissues in order to provide high quality samples for detailed analysis by chemical analysis sites. Tissues were collected from 10-12 rats sedentary control rats concurrent with the collection of the 8-week training groups. The 8-week training group and controls were from the same cohort and same age at euthanasia. For the older age group, an additional set of controls (n=5-6) were collected with the 1-2 week training group. Rats were either sedentary or underwent an exercise training program. Rats were exercised on the rodent treadmill 5 days per week using a progressive training protocol designed to exercise the rats at approximately 70% of VO2max and training was performed no earlier than 10:00 am and no later than 5:00 pm over 5 consecutive days per week. Training was initiated with the treadmill set at 70% of VO2 max and 5 degrees grade for 20 minutes. The duration of exercise was increased by one minute each day until day 31 of training (start of week 7), when a duration of 50 min was reached. Speed and grade of each training session increased in larger increments due to treadmill parameters. The highest intensity and duration of training began on day 31. This intensity was maintained for the final 10 days of the protocol to ensure steady state had been achieved. If any rats were unable to perform at least 4 days of training per week they were removed from the study and euthanized. It is important to note that the starting treadmill speed varied depending on the sex and age of the rat. The initial and maximum speeds were based on VO2max measurements obtained during the pre-training testing of the compliant rats. Rats assigned to the control group followed a schedule similar to the training group. They were placed in one lane on the treadmill for 15 minutes/day, 5 days per week. The treadmill was set at 0 m/min at an incline that corresponded to the incline being used by the training group.
2023-09-30 | GSE242357 | GEO
Project description:The goal of the endurance exercise training study in young adult rats was to perform exercise training studies in young adult (6-month-old) F344 rats, and from these rats collect multiple tissues in order to provide high quality samples for detailed analysis by chemical analysis sites. Tissues were collected from 10-12 rats sedentary control rats concurrent with the collection of the 8-week training groups. The 8-week training group and controls were from the same cohort and same age at euthanasia. For the older age group, an additional set of controls (n=5-6) were collected with the 1-2 week training group. Rats were either sedentary or underwent an exercise training program. Rats were exercised on the rodent treadmill 5 days per week using a progressive training protocol designed to exercise the rats at approximately 70% of VO2max and training was performed no earlier than 10:00 am and no later than 5:00 pm over 5 consecutive days per week. Training was initiated with the treadmill set at 70% of VO2 max and 5 degrees grade for 20 minutes. The duration of exercise was increased by one minute each day until day 31 of training (start of week 7), when a duration of 50 min was reached. Speed and grade of each training session increased in larger increments due to treadmill parameters. The highest intensity and duration of training began on day 31. This intensity was maintained for the final 10 days of the protocol to ensure steady state had been achieved. If any rats were unable to perform at least 4 days of training per week they were removed from the study and euthanized. It is important to note that the starting treadmill speed varied depending on the sex and age of the rat. The initial and maximum speeds were based on VO2max measurements obtained during the pre-training testing of the compliant rats. Rats assigned to the control group followed a schedule similar to the training group. They were placed in one lane on the treadmill for 15 minutes/day, 5 days per week. The treadmill was set at 0 m/min at an incline that corresponded to the incline being used by the training group.
2023-09-30 | GSE242355 | GEO
Project description:The goal of the endurance exercise training study in young adult rats was to perform exercise training studies in young adult (6-month-old month) F344 rats, and from these rats collect multiple tissues in order to provide high quality samples for detailed analysis by chemical analysis sites. Tissues were collected from 10-12 rats sedentary control rats concurrent with the collection of the 8-week training groups. The 8-week training group and controls were from the same cohort and same age at euthanasia. For the older age group, an additional set of controls (n=5-6) were collected with the 1-2 week training group. Rats were either sedentary or underwent an exercise training program. Rats were exercised on the rodent treadmill 5 days per week using a progressive training protocol designed to exercise the rats at approximately 70% of VO2max and training was performed no earlier than 10:00 am and no later than 5:00 pm over 5 consecutive days per week. Training was initiated with the treadmill set at 70% of VO2 max and 5 degrees grade for 20 minutes. The duration of exercise was increased by one minute each day until day 31 of training (start of week 7), when a duration of 50 min was reached. Speed and grade of each training session increased in larger increments due to treadmill parameters. The highest intensity and duration of training began on day 31. This intensity was maintained for the final 10 days of the protocol to ensure steady state had been achieved. If any rats were unable to perform at least 4 days of training per week they were removed from the study and euthanized. It is important to note that the starting treadmill speed varied depending on the sex and age of the rat. The initial and maximum speeds were based on VO2max measurements obtained during the pre-training testing of the compliant rats. Rats assigned to the control group followed a schedule similar to the training group. They were placed in one lane on the treadmill for 15 minutes/day, 5 days per week. The treadmill was set at 0 m/min at an incline that corresponded to the incline being used by the training group.
2023-09-30 | GSE242354 | GEO
Project description:Interventions: This multi-centre dose escalation study is designed to assess the safety and efficacy of a single implant of SIR-Spheres when given in combination with the first line chemotherapy combination consisting of irinotecan, 5-fluorouracil and leucovorin. The chemotherapy will be administered on weeks 1 and 2 of a 3 week cycle and given for 3 cycles. The irinotecan will then be escalated to the standard dose and an additional 6 cycles of chemotherapy will be administered.
Primary outcome(s): Toxicity[Assessed up to 1 month after the conclusion of protocol chemotherapy];Response rate[Assessed up until the scan after the conclusion of protocol chemotherapy]
Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy
| 2452596 | ecrin-mdr-crc