Systemic Therapy in Combination with Stereotactic Radiotherapy in Patients with Metastatic Colorectal Cancer Up to 10 Metastatic Sites

NCT05375708 | Suspended Phase 2 DMC

• 1 other identifier: NL76444.041.21
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer; Oligometastatic Disease

Keywords

Metastatic colorectal cancer; Image guided radiation; MR guided therapy; Oligometastatic / polymetastatic cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Defined as time from randomization to progression of disease or death, whichever occurs first. Progression of disease is based on tumor response as observed on radiographic imaging according to the RECIST 1.1 criteria.

  Through study completion, an average of 24 months

Secondary Outcomes (11)

• Accrual rate as assessed by the number of patients included in the study compared to the expected accrual rate.

  Through study completion, an average of 24 months

• Treatment success rate

  Through study completion, an average of 24 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Through study completion, an average of 24 months

• Overall survival

  Up to 72 months

• Comparing changes on health-related quality of life based on summary score of Quality of Life Questionnaire-Core30 (QLQ-C30) from baseline and 3-monthly timepoints.

  Through study completion, an average of 24 months

Study Arms (2)

Systemic maintenance therapy

ACTIVE COMPARATOR

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

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

EXPERIMENTAL

Radiation: Stereotactic body radiation therapy (SBRT); Drug: Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.)

Interventions

Stereotactic body radiation therapy (SBRT) RADIATION

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.

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

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

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.

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

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (4)

Meander Medical Centre

Amersfoort, Utrecht, 3813TZ, Netherlands

Location

St. Antonius

Utrecht, Utrecht, 3543AZ, Netherlands

Location

Diakonessenhuis

Utrecht, Utrecht, 3582KE, Netherlands

Location

UMC Utrecht

Utrecht, Utrecht, 3584CX, Netherlands

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiosurgery; Maintenance; Bevacizumab

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Health Care Facilities Workforce and Services; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Guus Bol, Dr.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Martijn Intven, Dr.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Miriam Koopman, Prof. Dr.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: May 17, 2022
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2034
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

NL (4)