Systemic Therapy in Combination with Stereotactic Radiotherapy in Patients with Metastatic Colorectal Cancer Up to 10 Metastatic Sites
- Conditions
- Metastatic Colorectal CancerOligometastatic Disease
- Interventions
- Radiation: Stereotactic body radiation therapy (SBRT)Drug: Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.)
- Registration Number
- NCT05375708
- Lead Sponsor
- UMC Utrecht
- 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.
- Detailed Description
The addition of stereotactic body radiation therapy (SBRT) to metastases in a limited unresectable metastatic setting might improve progression-free survival (PFS). The success of the addition of local treatments in mCRC patients depends largely on: control of microscopic disease, diagnostic accuracy of macroscopic disease and effective treatment of all detected metastases with limited additional toxicity to surrounding tissues. Until shortly, the use of SBRT was possible to a limited number of locations due to target movement or toxicity to surrounding radiosensitive structures. With the introduction of MRI-guided radiotherapy these limitations have been largely reduced due to the possibility to make a daily new treatment plan based on MRI-visualized anatomy. This allows the use of smaller margins for uncertainty with less healthy tissues in the radiation field. Thereby, a broader application of SBRT to add local control to metastases became possible.
This study is an open-label, multicenter, randomized phase II screening trial assessing the impact of SBRT in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with mCRC and ≤10 metastases with no option of local treatment with curative intent and with stable disease or partial response after treatment of CAPOX-B, FOLFOX-B or FOLFOXIRI-B.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 93
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT) Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.) - Systemic maintenance therapy Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.) - Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT) Stereotactic body radiation therapy (SBRT) -
- Primary Outcome Measures
Name Time Method Progression-free survival Through study completion, an average of 24 months 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.
- Secondary Outcome Measures
Name Time Method 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 We expect to include 93 patients in 24 months. The expected accrual rate in this study is, therefore, around 4 patients per month. Information for the accrual rate is used from the total accrual rate, the accrual rate in each study center and screening failures.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 Through study completion, an average of 24 months This will be based on the number of patients with SBRT related toxicity, defined as newly developed grade 2 toxicity of specific interest and grade 3-4 toxicity since randomization according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Overall survival Up to 72 months Defined as time from randomization to death of any cause.
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 EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score is better level of functioning.
Comparing changes on health-related quality of life based on summary score of Quality of Life Questionnaire-Core29 (QLQ-C29) from baseline and 3-monthly timepoints. Through study completion, an average of 24 months EORTC QLQ-C30 is a 29-item questionnaire to assess the overall quality of life in cancer patients. All questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score is better level of functioning.
Pattern of reccurence according to RECIST 1.1: New metastatic lesions, progression of existing lesions or a combination. Through study completion, an average of 24 months New metastatic lesions, progression of existing lesions or a combination of both new metastatic lesions and progression of existing lesions based on radiographic imaging according to RECIST 1.1
Comparing changes from health-related quality of life based on summary score of Multidimensional Fatigue Inventory (MFI-20) from baseline and 3-monthly timepoints. Through study completion, an average of 24 months MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue).
Time to treatment failure Through study completion, an average of 24 months Defined as the time of randomization to failure of treatment. If radiologically visible metastatic lesions before systemic therapy are no longer visible at randomization (vanishing lesions) and recurrence of vanishing lesions occurs in patients in the experimental arm without progression of other lesions, this is not yet determined as failure of treatment; additional local therapy is highly encouraged on these lesions (to the discretion of the local investigator). When progression of existing lesions or new lesions occur, it will be determined as failure of treatment.
Tumor response Through study completion, an average of 24 months Based on radiographic imaging according to the RECIST 1.1 criteria.
Depth of response Through study completion, an average of 24 months Based on radiographic imaging
Treatment success rate Through study completion, an average of 24 months Dose intensity of SBRT based on the number of patients that receive more than 90% of the planned dose on all lesions in 95% of the planned target volume (PTV).
Trial Locations
- Locations (4)
Meander Medical Centre
🇳🇱Amersfoort, Utrecht, Netherlands
St. Antonius
🇳🇱Utrecht, Netherlands
Diakonessenhuis
🇳🇱Utrecht, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands