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

NCT03532204 | Withdrawn DMC

• 1 other identifier: UC-0107/1602
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Liver Metastases; Colorectal Cancer

Keywords

Oligometastatis; SBRT

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1

  1 year

Secondary Outcomes (6)

• Local Control rate

  1 and 3 years

• Overall survival

  3 years

• Cancer specific survival

  3 years

• CTCAE Toxicity Assessment

  up to 24 weeks

• Quality of life EORTC QLQ C30

  up to 24 weeks

Study Arms (2)

Chemotherapy + SBRT

EXPERIMENTAL

Patients will received 2 courses of chemotherapy before SBRT if no hepatic or extra-hepatic progression identified. All liver metastases will be irradiated. 4 doses prescription are allowed (according to the center, and the technique uded and the dosimetric constraints): 3x15 Gy, 4 x 15 Gy, 5 x10 Gy or 5 x 8 Gy. The remaining courses of chemotherapy 2 to 3 weeks after completion of SBRT will be administered

Radiation: SBRT; Drug: Chemotherapy

Chemotherapy

ACTIVE COMPARATOR

Patients will receive chemotherapy as initially scheduled

Drug: Chemotherapy

Interventions

SBRT RADIATION

Patients will received 2 courses of chemotherapy before SBRT if no hepatic or extra-hepatic progression identified. All liver metastases will be irradiated. 4 doses prescription are allowed (according to the center, and the technique uded and the dosimetric constraints): 3x15 Gy, 4 x 15 Gy, 5 x10 Gy or 5 x 8 Gy. The remaining courses of chemotherapy 2 to 3 weeks after completion of SBRT will be administered

Chemotherapy + SBRT

Chemotherapy DRUG

At investigator's discretion

Chemotherapy; Chemotherapy + SBRT

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with age ≥18 years and \<85 years;
• Patient with histologically proven colorectal cancer;
• Patient with a curative surgical treatment (R0) of the primary tumor performed;
• Oligometastatic disease defined as 1 to 3 liver-only metastases (measurable lesion as per RECIST 1.1);
• Patient unfit for surgery or with unresectable metastases;
• Maximal diameter of largest metastasis: 30 mm;
• 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);
• WHO status 0-1;
• Adequate liver function: bilirubin \<3 mg/dL, albumin \>2.5 g/dL;
• Adequate hematological function: absolute neutrophil count (ANC) \>1.5 x 10⁹/L; platelets \>100 x 10⁹/L, hemoglobin (Hb) \>9 g/dL;
• Normal PT (\>70%) and PTT except if the patient uses anticoagulants;
• Liver enzymes \<3 times upper limit of normal;
• Renal function must be adequate for infusion of iv. contrast agent for CT-scan according to the local policy;
• 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;
• Patient who have received the information sheet, dated and signed the informed consent form;

You may not qualify if:

• Healthy liver volume\<700 mL
• Life expectancy \<3 months;
• Patient fit for metastasectomy or hepatectomy;
• Extrahepatic metastases;
• Cirrhosis with Child Pugh score B or C;
• More than one line of chemotherapy in the metastatic setting or rapidly progressing disease;
• Previous local treatment of liver metastases;
• Treatment with any other investigational agent against cancer;
• 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;
• Pregnant woman or breast feeding mother;
• 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.).

Sponsors & Collaborators

• UNICANCER: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Stéphanie SERVAGI, MD

  INSTITUT JEAN GODINOT, REIMS

  PRINCIPAL INVESTIGATOR

• Gilles CREHANGE, MD

  CENTRE GEORGES FRANCOIS LECLERC, DIJON

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: May 22, 2018
• Study Start: April 15, 2019
• Primary Completion: December 15, 2021
• Study Completion: August 15, 2023
• Last Updated: May 22, 2019

Record last verified: 2019-05