Clinical trial

A Multicenter Phase II Randomized Trial to Evaluate Systemic Therapy Versus Systemic Therapy in Combination With Stereotactic Radiotherapy in Patients With Metastatic Colorectal Cancer

Name

NL76444.041.21

Description

A small number of colorectal cancer patients with limited oligometastases may be candidates for local treatment of metastases (e.g., resection, ablation). However, it is unclear if patients with more extensive metastatic disease benefit from local therapies to control visible metastasis. The purpose of this study is to assess the impact of stereotactic body radiation therapy (SBRT) in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with metastatic colorectal cancer (mCRC) and ≤10 metastases.

Trial arms

Trial start

2024-06-01

Estimated PCD

2028-06-01

Trial end

2028-06-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

Stereotactic body radiation therapy (SBRT)

Patients will receive a single fraction of 15 Gy to each of the macroscopic tumor sites including the primary tumor if still in situ. All lesions are treated. The treatment will be delivered in an image-guided way, either on a conventional linear accelerator (LINAC) or a MR-LINAC, whichever has the best targeting according to the treating radiation oncologist.

Arms:

Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT)

Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.)

CAP + bevacizumab (following CAPOX-B) Bevacizumab 7.5mg/kg i.v. on day 1 and 1250 mg/m2 of capecitabine, orally twice daily on days 1-14 if age is \<70 years and 1000 mg/m2 of capecitabine, orally twice daily on days 1-14 if age is higher than 70 years. CAP + bevacizumab is repeated every three weeks. 5-FU/LV + bevacizumab (following FOLFOX-B) Bevacizumab 5.0mg/kg i.v. together with leucovorin 400 mg/m2 i.v. bolus 5FU 400 mg/m2 all on day 1. Followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours. 5-FU + bevacizumab is repeated every two weeks. 5-FU/LV + bevacizumab (following FOLFOXIRI-B) Bevacizumab 5.0mg/kg i.v. together with leucovorin 400 mg/m2 i.v. all on day 1. Followed by continuous infusion of 5-fluorouracil 3200 mg/m2 in 46 hours. 5-FU + bevacizumab is repeated every two weeks. When S1 is used a replacement for fluoropyrimidine therapy it is administered in a dose of 30mg/m2 twice daily on days 1-14. S1 is repeated every three weeks.

Arms:

Systemic maintenance therapy, Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT)

Size

Primary endpoint

Progression-free survival

Through study completion, an average of 24 months

Eligibility criteria

Inclusion Criteria: * Registered in the prospective Dutch colorectal cancer cohort (PLCRC) * Intention at start of palliative systemic therapy to receive six maximum tolerated dose (MTD) cycles of CAPOX-B or eight MTD cycles of FOLFOX-B or FOLFOXIRI-B. * Ten or less metastases as determined by the university medical center Utrecht (UMCU) central review * Stable disease or partial response after initial chemotherapy according to RECIST 1.1 criteria. * Expected adequacy of follow-up * World Health organization (WHO) performance status 0-1 * Life expectancy \>12 weeks * Adequate organ functions at start of initial therapy, as determined by normal bone marrow function (Hb≥6.0 mmol/L, absolute neutrophil count ≥1.5 x 10\^9/L, platelets ≥100 x 10\^9/L), renal function (serum creatinine ≤ 1.5x upper limit of normal (ULN) and creatinine clearance, Cockcroft formula, ≥30 ml/min) and liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases) * Written informed consent (SIRIUS) Exclusion Criteria: * Less than three cycles of CAPOX-B or four cycles of FOLFOX-B or FOLFOXIRI-B (dose reductions allowed). * More than six cycles of CAPOX-B or eight cycles of FOLFOX-B of FOLFOXIRI-B. * Possible treatment with curative intent according to local tumor board * Substantial overlap with a previously treated radiation volume. Previous radiotherapy is allowed as long as the composite plan meets dose constraints herein. * Not amenable for radiotherapy (e.g. peritonitis carcinomatosa) * Previous systemic treatment for metastatic disease; prior adjuvant treatment for stage II/III colorectal cancer when given \>6 months before the start of initial systemic treatment is allowed. * Serious comorbidity or any other condition preventing the safe administration of treatment (including both systemic treatment and radiation) * Pregnant or lactating women * Other malignancy interfering with prognosis * Any concomitant experimental treatment. * Contra-indication MR-LINAC (pacemaker or implantable cardioverter-defibrillator) * Microsatellite instability or deficient mismatch repair tumor

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 93, 'type': 'ESTIMATED'}}

Updated at

2023-05-11

1 organization

1 product

2 indications

Organization

UMC Utrecht

Product

Maintenance therapy

Indication

Colorectal Cancer

Indication

Oligometastatic Disease