Clinical trial NCT03532204: Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
Official title: Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Liver Metastases
Colorectal Cancer
Keywords: Oligometastatis
SBRT
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2018-05-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The role of radiotherapy in metastatic cancer has historically been limited to palliation while metastasectomy or radiofrequency has emerged as playing a major role in disease control. Although resection is the standard of care for liver metastasis, 80-90% of patients are not resectable at diagnosis in particular because of the presence of oligometastases. Factors that favour a truly oligometastatic state include a long latent interval between the treatment of the primary tumor and the appearance of metastases.

Oligometastatic cancer is a very heterogeneous disease with respect to several factors including the location of the primary tumor. With the advent of extracranial stereotactic body radiation therapy (SBRT), higher biological equivalent doses can be safely delivered in 3 to 5 fractions, thus potentially ablating all the tissue in the treated area while protecting more efficiently the hosting organ and healthy tissues surrounding the tumors.

In patients with liver oligometastases, in-field local control rates at 2 years range from 70% to 90% with less than 5% severe grade 3 or higher toxicity rates. Retrospective studies indicate that roughly 20% of the patients remain disease-free 2 to 4 years after SBRT.

For patients treated with SBRT some authors found that half of the patients had either no metastatic progression or very little progression in terms of number and site of metastases. The patterns of failure after SBRT for oligometastases in one organ showed that 73% of patients eventually developed new metastases with higher than 80% occurring as new metastases in the same index organ. These findings support the idea of an oligometastatic state in which aggressive local therapy could improve progression-free survival (PFS).

With this phase III study, we sought to evaluate the impact of SBRT on PFS at 2 years in patients with synchronous or metachronous liver-only oligometastases from colorectal cancers patients after a first line chemotherapy for metastatic disease but not having progressed during first line chemotherapy and up to 1 year


Eligibility criteria: Inclusion Criteria:

1. Male or female with age ≥18 years and \<85 years;
2. Patient with histologically proven colorectal cancer;
3. Patient with a curative surgical treatment (R0) of the primary tumor performed;
4. Oligometastatic disease defined as 1 to 3 liver-only metastases (measurable lesion as per RECIST 1.1);
5. Patient unfit for surgery or with unresectable metastases;
6. Maximal diameter of largest metastasis: 30 mm;
7. Patient naïve of chemotherapy in the metastatic setting or after a first-line of chemotherapy for metastatic disease but not having progressed up to 1 year (i.e. slowly progressing disease);
8. WHO status 0-1;
9. Adequate liver function: bilirubin \<3 mg/dL, albumin \>2.5 g/dL;
10. Adequate hematological function: absolute neutrophil count (ANC) \>1.5 x 10⁹/L; platelets \>100 x 10⁹/L, hemoglobin (Hb) \>9 g/dL;
11. Normal PT (\>70%) and PTT except if the patient uses anticoagulants;
12. Liver enzymes \<3 times upper limit of normal;
13. Renal function must be adequate for infusion of iv. contrast agent for CT-scan according to the local policy;
14. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study and up to 3 months following completion of therapy;
15. Patient who have received the information sheet, dated and signed the informed consent form;
16. Affiliated to the social security system.

Exclusion Criteria:

1. Healthy liver volume\<700 mL
2. Life expectancy \<3 months;
3. Patient fit for metastasectomy or hepatectomy;
4. Extrahepatic metastases;
5. Cirrhosis with Child Pugh score B or C;
6. More than one line of chemotherapy in the metastatic setting or rapidly progressing disease;
7. Previous local treatment of liver metastases;
8. Treatment with any other investigational agent against cancer;
9. Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent;
10. Pregnant woman or breast feeding mother;
11. Patient deprived of liberty or placed under the authority of a tutor. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Patient unable to understand the purpose of the study (language, etc.).

Primary outcomes:
measure: Progression Free Survival
timeFrame: 1 year
Secondary outcomes:
measure: Local Control rate
timeFrame: 1 and 3 years
measure: Overall survival
timeFrame: 3 years
measure: Cancer specific survival
timeFrame: 3 years
measure: CTCAE Toxicity Assessment
timeFrame: up to 24 weeks
measure: Quality of life EORTC QLQ C30
timeFrame: up to 24 weeks
measure: Quality of life EORTC QLQ CR29
timeFrame: up to 24 weeks
Other outcomes:
Locations:
Study officials:
affiliation: INSTITUT JEAN GODINOT, REIMS
name: Stéphanie SERVAGI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CENTRE GEORGES FRANCOIS LECLERC, DIJON
name: Gilles CREHANGE, MD
role: PRINCIPAL_INVESTIGATOR
References: