OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer

Официальное название

OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer - a ctDNA Guided Phase II Randomized Approach

Обзор

A study investigating if analysis of circulating tumor DNA (ctDNA) can guide adjuvant treatment in patients with advanced colorectal cancer (CRC)

Подробное описание

An open label 1:1 randomized phase II exploratory study investigating use of ctDNA-guided adjuvant chemotherapy compared to standard of care (SOC) after local treatment for metastatic colorectal cancer.

Patients are randomized 1:1 between SOC and ctDNA guided treatment and follow-up.

Escalation therapy comprises standard regimen of Fluorouracil (5-FU), Irinotecan and oxaliplatin (FOLFOXIRI), de-escalation therapy of monotherapy capecitabine or observation only. SOC is per institutional practice, based on national guidelines.

Вмешательства

• Другое Standard of care
  Patients will be offered adjuvant chemotherapy according to standard of care. Follow up will be performed with imaging according to standard guidelines, equal to the experimental arm. Blood samples will be analyzed retrospectively to evaluate the ctDNA status.
• Другое Circulating tumor DNA guided treatment approach
  Circulating tumor-marker positivity will lead to escalation with 6 months of intensified chemotherapy consisting of 4 months of FOLFOXIRI followed by 2 months of 5FU monotherapy. Circulating tumor-marker negativity will based on shared decision-making lead to de-escalation i.e. possibilities for observation in patients otherwise eligible for monotherapy or observation/monotherapy in patients, otherwise eligible for combination chemotherapy according to standard of care.

Первичные конечные точки

• Recurrence Free Rate [Срок оценки: 2 years]

Вторичные конечные точки (10)

• Toxicity of treatment [Срок оценки: 6 months post-treatment]
• Molecular biological response to therapy [Срок оценки: 6 months post-treatment]
• Molecular biological Disease Free Survival [Срок оценки: 1 year from inclusion]
• Time to molecular biological recurrence [Срок оценки: 5 years last patient]
• Time to radiological recurrence [Срок оценки: 5 years last patient]
• Local and distant relapse [Срок оценки: 5 years last patient]
• Overall survival [Срок оценки: 5 years last patient]
• Quality of life according to EORTC QLQ-CR29 and -C30 [Срок оценки: 5 years last patient]
• Quality of life according to EQ-5D-5L [Срок оценки: 5 years last patient]
• Cost-effectiveness analysis [Срок оценки: 5 years last patient]

Критерии участия

Критерии включения

• Radical intended treatment for metastatic spread from CRC, by resection, radiofrequency ablation, stereotactic body radiation therapy (or other experimental local treatment options) not including cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC)
• No evidence of further disease based on pre-treatment work-up according to SOC
• Age at least 18 years
• Eastern Cooperative Oncology Group performance status 0-2
• Clinically eligible for adjuvant triple CT at investigators decision.
• Adequate bone marrow, liver and renal function allowing systemic chemotherapy (Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l. Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value, and calculated or measured renal glomerular filtration rate at least 30 mL/min)
• Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable
• Written and verbally informed consent

Критерии исключения

• Radiological evidence of distant metastasis, by CT- chest, abdomen, and pelvis
• Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with triple combination chemotherapy
• Neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade > 1
• Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
• Pregnant (positive pregnancy test) or breast feeding women
• Intolerance or allergy to 5FU, leucovorin, oxaliplatin, irinotecan or capecitabine

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Дания · 2 центра

• Department of Oncology, Aarhus University Hospital — Aarhus N
• Department pf Oncology, Vejle Hospital — Vejle

Идентификаторы

NCT: NCT04680260 · KFE2022

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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