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Systemic Therapy in Combination With Stereotactic Radiotherapy in Patients With Metastatic Colorectal Cancer up to 10 Metastatic Sites

Studies

Study First Submitted Date 2022-04-05
Study First Posted Date 2022-05-17
Last Update Posted Date 2023-05-11
Start Month Year June 1, 2024
Primary Completion Month Year June 1, 2028
Verification Month Year May 2023
Verification Date 2023-05-31
Last Update Posted Date 2023-05-11

Detailed Descriptions

Sequence: 20578090
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.

Facilities

Sequence: 198659300 Sequence: 198659301 Sequence: 198659302 Sequence: 198659303
Name Meander Medical Centre Name St. Antonius Name Diakonessenhuis Name UMC Utrecht
City Amersfoort City Utrecht City Utrecht City Utrecht
State Utrecht
Zip 3813TZ Zip 3543AZ Zip 3582KE Zip 3584CX
Country Netherlands Country Netherlands Country Netherlands Country Netherlands

Facility Contacts

Sequence: 27944290 Sequence: 27944291 Sequence: 27944292 Sequence: 27944293
Facility Id 198659300 Facility Id 198659301 Facility Id 198659302 Facility Id 198659303
Contact Type primary Contact Type primary Contact Type primary Contact Type primary
Name Hans-Martin Otten, Dr. Name Maartje Los, Dr. Name Tanja Oostergo, Dr. Name Koen Zwart, Drs.
Email SIRIUS@umcutrecht.nl
Phone 088-7556084

Browse Interventions

Sequence: 95328422 Sequence: 95328423 Sequence: 95328424 Sequence: 95328425 Sequence: 95328426 Sequence: 95328427 Sequence: 95328428 Sequence: 95328429
Mesh Term Bevacizumab Mesh Term Antineoplastic Agents, Immunological Mesh Term Antineoplastic Agents Mesh Term Angiogenesis Inhibitors Mesh Term Angiogenesis Modulating Agents Mesh Term Growth Substances Mesh Term Physiological Effects of Drugs Mesh Term Growth Inhibitors
Downcase Mesh Term bevacizumab Downcase Mesh Term antineoplastic agents, immunological Downcase Mesh Term antineoplastic agents Downcase Mesh Term angiogenesis inhibitors Downcase Mesh Term angiogenesis modulating agents Downcase Mesh Term growth substances Downcase Mesh Term physiological effects of drugs Downcase Mesh Term growth inhibitors
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Conditions

Sequence: 51800522 Sequence: 51800523
Name Metastatic Colorectal Cancer Name Oligometastatic Disease
Downcase Name metastatic colorectal cancer Downcase Name oligometastatic disease

Id Information

Sequence: 39863840
Id Source org_study_id
Id Value NL76444.041.21

Countries

Sequence: 42261312
Name Netherlands
Removed False

Design Groups

Sequence: 55220353 Sequence: 55220354
Group Type Active Comparator Group Type Experimental
Title Systemic maintenance therapy Title Systemic maintenance therapy in combination with stereotactic body radiation therapy (SBRT)

Interventions

Sequence: 52122593 Sequence: 52122594
Intervention Type Radiation Intervention Type Drug
Name Stereotactic body radiation therapy (SBRT) Name Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.)
Description 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. Description 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.

Keywords

Sequence: 79260625 Sequence: 79260626 Sequence: 79260627 Sequence: 79260628
Name Metastatic colorectal cancer Name Image guided radiation Name MR guided therapy Name Oligometastatic / polymetastatic cancer
Downcase Name metastatic colorectal cancer Downcase Name image guided radiation Downcase Name mr guided therapy Downcase Name oligometastatic / polymetastatic cancer

Design Outcomes

Sequence: 176182147 Sequence: 176182148 Sequence: 176182149 Sequence: 176182150 Sequence: 176182151 Sequence: 176182152 Sequence: 176182153 Sequence: 176182154 Sequence: 176182155 Sequence: 176182156 Sequence: 176182157 Sequence: 176182158
Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary
Measure Progression-free survival Measure Accrual rate as assessed by the number of patients included in the study compared to the expected accrual rate. Measure Treatment success rate Measure Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 Measure Overall survival Measure 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. Measure 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. Measure Comparing changes from health-related quality of life based on summary score of Multidimensional Fatigue Inventory (MFI-20) from baseline and 3-monthly timepoints. Measure Pattern of reccurence according to RECIST 1.1: New metastatic lesions, progression of existing lesions or a combination. Measure Time to treatment failure Measure Tumor response Measure Depth of response
Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Up to 72 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months Time Frame Through study completion, an average of 24 months
Description 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. Description 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. Description 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). Description 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) Description Defined as time from randomization to death of any cause. Description 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. Description 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. Description 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). Description 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 Description 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. Description Based on radiographic imaging according to the RECIST 1.1 criteria. Description Based on radiographic imaging

Browse Conditions

Sequence: 191993844 Sequence: 191993845 Sequence: 191993846 Sequence: 191993847 Sequence: 191993848 Sequence: 191993849 Sequence: 191993850 Sequence: 191993851 Sequence: 191993852 Sequence: 191993853 Sequence: 191993854
Mesh Term Colorectal Neoplasms Mesh Term Intestinal Neoplasms Mesh Term Gastrointestinal Neoplasms Mesh Term Digestive System Neoplasms Mesh Term Neoplasms by Site Mesh Term Neoplasms Mesh Term Digestive System Diseases Mesh Term Gastrointestinal Diseases Mesh Term Colonic Diseases Mesh Term Intestinal Diseases Mesh Term Rectal Diseases
Downcase Mesh Term colorectal neoplasms Downcase Mesh Term intestinal neoplasms Downcase Mesh Term gastrointestinal neoplasms Downcase Mesh Term digestive system neoplasms Downcase Mesh Term neoplasms by site Downcase Mesh Term neoplasms Downcase Mesh Term digestive system diseases Downcase Mesh Term gastrointestinal diseases Downcase Mesh Term colonic diseases Downcase Mesh Term intestinal diseases Downcase Mesh Term rectal diseases
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 47973855
Agency Class OTHER
Lead Or Collaborator lead
Name UMC Utrecht

Overall Officials

Sequence: 29066606 Sequence: 29066607 Sequence: 29066608
Role Principal Investigator Role Principal Investigator Role Principal Investigator
Name Guus Bol, Dr. Name Martijn Intven, Dr. Name Miriam Koopman, Prof. Dr.
Affiliation UMC Utrecht Affiliation UMC Utrecht Affiliation UMC Utrecht

Central Contacts

Sequence: 11933636 Sequence: 11933637
Contact Type primary Contact Type backup
Name Koen Zwart, Drs. Name Guus Bol, Dr.
Phone 088-7556084
Email SIRIUS@Umcutrecht.nl Email G.M.Bol-2@umcutrecht.nl
Role Contact Role Contact

Design Group Interventions

Sequence: 67700794 Sequence: 67700795 Sequence: 67700796
Design Group Id 55220354 Design Group Id 55220353 Design Group Id 55220354
Intervention Id 52122593 Intervention Id 52122594 Intervention Id 52122594

Eligibilities

Sequence: 30547765
Gender All
Minimum Age 18 Years
Maximum Age N/A
Healthy Volunteers No
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
Adult True
Child False
Older Adult True

Calculated Values

Sequence: 254215472
Number Of Facilities 4
Registered In Calendar Year 2022
Were Results Reported False
Has Us Facility False
Has Single Facility False
Minimum Age Num 18
Minimum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 11

Designs

Sequence: 30296148
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking None (Open Label)

Responsible Parties

Sequence: 28674706
Responsible Party Type Principal Investigator
Name Guus Bol
Title Principal investigator
Affiliation UMC Utrecht