Oligometastases of the Liver Treated With Chemotherapy With or Without Radiotherapy in Patients With Colorectal Cancer

Last updated: N/A
Sponsor: UNICANCER
Overall Status: Active - Not Recruiting

Phase

3

Condition

Colon Cancer; Rectal Cancer

Cancer

Colon Cancer

Treatment

N/A

Clinical Study ID

NCT03296839
UC-0107/1602
  • Ages 18-84
  • All Genders

Study Summary

Colorectal cancer is a major cause of morbidity and mortality throughout the world and accounts for more than 9% of all cancer outcomes. Global mortality from colorectal cancer is approximately half the incidence. An estimated 394,000 colorectal cancer deaths occur worldwide each year, making colorectal cancer the fourth most common cause of cancer death. Overall survival rates after surgical resection of hepatic colorectal metastases were 10-18% higher than in patients treated with systemic therapy. Hepatic metastases occur in 45% of patients with colorectal cancer. Surgery is the standard of care for resectable diseases, with overall survival rates of 5 years (OS) of 28% -58%. Unfortunately, only 10-20% of patients have a resectable disease at the time of diagnosis. The current approach to treating nonresectable metastatic colorectal cancer (mCRC) promotes the use of combined cytotoxic therapy. First-line treatments include cytotoxic combinations. The role of radiotherapy in metastatic cancer is historically palliative, conventional radiotherapeutic techniques causing radiation-induced liver disease (RLID). With the advent of extracranial stereotactic radiotherapy (SBRT), equivalent doses can be safely administered in 3 to 5 fractions, which can result in the removal of all affected tissues in the treated area while limiting the irradiation of the host organ and the healthy tissues surrounding the tumors. The efficacy and safety of SBRT for liver metastases has been confirmed by retrospective studies showing local control rates of about 80% or more. Retrospective studies indicate that approximately 20% of patients remain disease-free 2 to 4 years after SBRT. For patients treated with SBRT, some authors found that half of the patients had no metastatic progression or very little progression in numbers and metastasis sites. These results confirm the idea of an oligometastatic state in which aggressive local therapy could improve progression-free survival (PFS). We propose in this study to evaluate the impact of SBRT on progression-free survival in patients with mCRC with 1-3 oligometastases of the liver. Two arms will be compared: the standard arm treated with chemotherapy; to the experimental arm combining chemotherapy and SBRT. The chemotherapy will be left free at the choice of the investigator according to the recommendations of national treatments.

Eligibility Criteria

Inclusion

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 asper 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 ofchemotherapy 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-scanaccording to the local policy;

  14. Woman of childbearing potential and male patients must agree to use adequatecontraception for the duration of study and up to 3 months following completion oftherapy;

  15. Patient who have received the information sheet, dated and signed the informed consentform;

  16. Affiliated to the social security system.

Exclusion

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 progressingdisease;

  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 foradequately treated carcinoma in situ of the cervix, basal or squamous cell skincancer, localized prostate cancer treated surgically with curative intent, and ductalcarcinoma 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 anypsychological, familial, sociological or geographical condition potentially hamperingcompliance with the study protocol and follow-up schedule; those conditions should bediscussed with the patient before registration in the trial. Patient unable tounderstand the purpose of the study (language, etc.).

Study Design

Total Participants: 210
Study Start date:
December 01, 2017
Estimated Completion Date:
January 31, 2023