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

Colorectal Cancer Clinical Trial

— OLIVER  

Official title:

Oligometastases of the LIVer Treated With Chemotherapy With or Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03296839
• Other study ID #: UC-0107/1602
• Status: Not yet recruiting
• Phase: Phase 3
• First received: September 25, 2017
• Last updated: October 4, 2017
• Start date: December 2017
• Est. completion date: January 2023

Study information

• Verified date: October 2017
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 210
• Est. completion date: January 2023
• Est. primary completion date: July 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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.).

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Liver Metastases
• Neoplasm Metastasis
• Radiation Therapy

Intervention

Radiation:
• SBRT
All liver metastases will be irradiated. 4 dose prescriptions are allowed (according to the center, and the technique used and the dosimetric constraints): 3 x 15 Gy, 4 x 15 Gy, 5 x 10 Gy or 5 x 8 Gy

Drug:
• Chemotherapy
The chemotherapy is left to the choice of the investigator

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival (PFS) at 2 years	To evaluate the impact of stereotactic body radiation therapy (SBRT) on progression-free survival (PFS) at 2 years in patients with liver oligometastases from colorectal cancer.	2 years
Secondary	local control rates	control rate in field	1 year
Secondary	local control rates	control rate in field	3 years
Secondary	liver PFS		1 year
Secondary	liver PFS		3 years
Secondary	overall survival	overall survival rates and median overall survival rates	3 years
Secondary	cancer-specific survival	cancer-specific survival and median cancer specific survival rates	3 years
Secondary	Incidence of SBRT toxicities	CTC AE 4.0	6 months
Secondary	Incidence of SBRT toxicities	CTC AE 4.0	3 years
Secondary	Quality of life	QLQ-C30 and QLQ-CR29	3 years
Secondary	salvage hepatic therapy	Any salvage hepatic therapy for intrahepatic failure (surgery, radiofrequency, SBRT, chemoembolization)	3 years
Secondary	ceramide and its sphingolipid metabolites	the predictive value of ceramide and its sphingolipid metabolites on long-term toxicity	3 years