Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Capecitabine

Bevacizumab

Cetuximab

Fluorouracil

Liver Extracts

Panitumumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Eligible patients will receive Scout dose procedure. After 1-2 weeks, patients eligible for radioembolization will receive 166Ho-TARE and at least after 3 weeks, maintenance treatment with fluoropyrimidine plus target agents (anti-EGFR or bevacizumab) according to the respective study cohort.

Maintenance treatment:

Cohort A:

* CETUXIMAB iv day1, over 1 hours, 500 mg/sqm or PANITUMUMAB iv over 1 hours, 6 mg/kg, every 14 days
* LED 200 mg/sqm iv over 1 hour, day 1
* 5-FLUOROURACIL ic 48 h, starting on day 1 every 14 days; 2400 mg/sqm and 400 mg/sqm bolus if FOLFOX/FOLFIRI in the induction treatment

Cohort B:

* BEVACIZUMAB 5 mg/kg iv biweekly day1, over 30 minutes
* LED 200 mg/sqm iv over 1 hour, day 1
* 5-FLUOROURACIL ic 48 h, starting on day 1 every 14 days; 2400 mg/sqm and 400 mg/sqm bolus if FOLFOX/FOLFIRI in the induction treatment

CAPECITABINE, 1000 mg/sqm orally twice daily, day 1-14, plus bevacizumab 7,5 mg/kg iv every 21 days is allowed.

166Ho-TARE treatment comprises of two hospital visits: one for a work-up procedure and another for the therapy procedure, with usually a 1-2 weeks interval.

166Holmium TARE

5-Fluorouracil

Gianluca Masi, MD

Laura Delliponti

Beatrice Borelli, MD, PhD

The aim of this study is to assess the efficacy of 166Ho-TARE followed by maintenance therapy with fluoropyrimidine and anti-EGFR or bevacizumab in liver-limited unresectable colorectal cancer patients, in terms of progression free rate 9- and 8-months for cohort A and B, respectively.

HAITI is a phase II, single-arm trial of 166Ho-TARE followed by maintenance therapy in liver-limited unresectable colorectal cancer patients, achieving partial response or stable disease according to RECIST 1.1 criteria after 6-12 cycles of induction first-line chemotherapy.

Two cohorts of patients are included:

* left sided RAS/BRAF wild-type (cohort A)
* right-sided and/or RAS mutated (cohort B)

Enrolled patients will be treated with different maintenance therapy according to study cohort (fluoropyrimidine + anti-EGFR or bevacizumab).

Two cohorts of patients will be included according to the two main prognostic populations in mCRC (left sided, RAS/BRAF wild-type and, right-sided and/or RAS mutated tumors) treated with different maintenance therapy (fluoropyrimidine plus anti-EGFR or bevacizumab).

A total of 23 patients will be enrolled in each cohort.

Holmium-166 TARE in Liver Limited Unresectable Colorectal Cancer Patients

Phase II Study Evaluating Holmium-166 TARE Followed by Maintenance Therapy in Liver Limited Unresectable Colorectal Cancer Patients After First-line Chemotherapy and Target Agents

PFS is defined as the time from study enrolment to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis.

Overall Toxicity rate is defined as the percentage of patients, relative to the total of enrolled subjects, who receive 166Ho-TARE and at least one cycle of chemotherapy, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0) during the study treatment.

Grade 3/ Grade 4 Toxicity rate is defined as the percentage of patients, relative to the total of enrolled subjects, who receive 166Ho-TARE and at least one cycle of chemotherapy, experiencing a specific adverse event of severity grade 3/ grade 4, according to National Cancer Institute Common Toxicity Criteria (version 5.0) during the study treatment.

Post-treatment DCR, is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR), partial (PR) response or stable disease (SD), according to RECIST 1.1 criteria, during the study treatment. The determination of clinical response will be based on investigator reported measurements. Tumor re-assessment with CT scan will be repeated every 8- weeks.

Progression free survival (PFS), is defined as the time from study enrolment to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis.

Overall Survival (OS), is defined as the time from enrolment to death from any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.

Dose-response relationships are defined as the relationships between the tumor-absorbed doses calculated on post-treatment SPECT-CT (dependent variables) and the following independent variables: tumor response (SD, PR, CR according to RECIST CRITERIA v 1.1), progression free survival rate, and Overall Survival.

The EORTC QLQ-CR29 is a patient-reported outcome measure to evaluate health-related quality of life among colorectal cancer patients in research and clinical practice.

QoL assessed using the EORTC QLQ-CR29 questionnaire will be evaluate at specific time-points (baseline, tumor reassessment and disease progression) and will be assessed through descriptive summary statistics.

The EORTC QLQ-CR30 is 30-item instrument designed to measure quality of life in all cancer patients.

QoL assessed using the EORTC QLQ-CR30 questionnaire will be evaluate at specific time-points (baseline, tumor reassessment and disease progression) and will be assessed through descriptive summary statistics.

The EuroQol EQ-5D comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.

QoL assessed using the EuroQol EQ-5D questionnaire will be evaluate at specific time-points (baseline, tumor reassessment and disease progression) and will be assessed through descriptive summary statistics.

Gruppo Oncologico del Nord-Ovest

SC-006 and ABBV-181 Combination escalation and expansion

SC-006

ABBV-181

AbbVie Inc.

This is a multicenter, open-label, Phase 1 study of SC-006 given as a single agent and in combination with ABBV-181 in participants with advanced colorectal cancer (CRC), and consists of Part A (single agent SC-006 dose regimen finding), followed by Part B (single agent SC-006 dose expansion), and Part C (SC-006 and ABBV-181 combination escalation and expansion). Part A (dose regimen finding) will involve dose escalation and possible dose interval modification to define the maximum tolerated dose (MTD) and/or recommended Part B dose and schedule. Part B (dose expansion) will enroll additional participants who will be treated with a study drug dose at or below the MTD determined in Part A. Part C is dose escalation of SC-006 and fixed dose of ABBV-181 in combination. Recommended dose cohort of SC-006 with ABBV-181 will be expanded.

A Study of SC-006 and in Combination With ABBV-181 in Subjects With Advanced Colorectal Cancer

An Open Label Phase 1 Study of SC-006 as a Single Agent and in Combination With ABBV-181 in Subjects With Advanced Colorectal Cancer

DLTs graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

OS is defined as the time from the participant's first dose date to death due to any cause.

PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death due to any cause.

Area under the plasma concentration-time curve within a dosing interval of SC-006

DOCB is defined as the time from the initial partial response (PR), complete response (CR), or stable disease to disease progression.

ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR), as determined by Investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression or death, whichever occurs first.

Observed plasma concentrations at trough of SC-006

CBR is defined as the percentage of participants who achieve a best response of CR, PR, or stable disease (SD).

Maximum observed serum concentration of SC-006

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Holmium-166 TARE in Liver Limited Unresectable Colorectal Cancer Patients	NCT06332079	Colorectal Canc...	166Holmium TARE Cetuximab Panitumumab 5-Fluorouracil Bevacizumab Capecitabine	18 Years -	Gruppo Oncologico del Nord-Ovest
Holmium-166 TARE in Liver Limited Unresectable Colorectal Cancer Patients	NCT06332079	Colorectal Canc...	166Holmium TARE Cetuximab Panitumumab 5-Fluorouracil Bevacizumab Capecitabine	18 Years -	Gruppo Oncologico del Nord-Ovest
A Study of SC-006 and in Combination With ABBV-181 in Subjects With Advanced Colorectal Cancer	NCT03035279	Colorectal Canc...	SC-006 ABBV-181	18 Years -	AbbVie

Spots Global Cancer Trial Database for unresectable colorectal cancer