Back to resultsIntraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab (INTERACT-II)
Primary Purpose
Colorectal Cancer, Peritoneal Metastases
Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Irinotecan
FOLFOX regimen
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Peritoneal metastases, colorectal cancer, Intraperitoneal, Irinotecan
Eligibility Criteria
Inclusion Criteria: Histologically confirmed colorectal cancer; Radiologically and clinically or pathologically confirmed unresectable colorectal peritoneal metastases (e.g. PCI >20, extensive small bowel involvement, unresectable disease due to anatomical location); WHO performance score of 0-1 with a life expectancy of >3 months; Aged 18 years or older; Written informed consent; Exclusion Criteria: Presence of extensive systemic metastases that are deemed to be the dominant factor determining prognosis in terms of life expectancy and performance status [e.g. no imminent threat of impaired organ functioning due to the presence of systemic metastases]); Prior cytoreductive surgery; Prior palliative systemic therapy for colorectal cancer; Prior neo-adjuvant/adjuvant systemic therapy for colorectal cancer within the last 6 months; Homozygous UGT1A1*28 genotype; Homozygous dihydropyrimidine dehydrogenase (DPD) deficiency Microsatellite instable (MSI) primary tumor Any contra-indication for the planned chemotherapy (e.g. active infection, serious concomitant disease, severe allergy), as determined by the medical oncologist; Inadequate organ functions, defined as an haemoglobin of <5 mmol/L, an absolute neutrophil count of <1.5 x 109/L, platelet count of <100 x 109/L, serum creatinine of >1.5 x ULN, creatinine clearance of <30 ml/min, Bilirubin > 2x ULN and liver transaminases of >5 x ULN.
Sites / Locations
- Catharina HospitalRecruiting
- Erasmus Medical CentreRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab
Arm Description
Intraperitoneal irinotecan, 75 mg flat dose + systemic oxaliplatin, 5-Fluorouracil and bevacizumab (mFOLFOX+beva) (dose via standard of care)
Outcomes
Primary Outcome Measures
Overall survival
calculated from (a) the interval from diagnosis of peritoneal metastases until death or last follow-up; (b) the interval from the first day of the first cycle until death or last follow-up).
Secondary Outcome Measures
Progression-free survival
calculated from the interval from the start of trial treatment until first evidence of intraperitoneal and/or systemic disease progression, and/or start of second-line systemic therapy, or last follow-up
Toxicity in CTCAE grading
Defined as the number of patients who experience / the total number of Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) grade 3-5 adverse events, measured up to four weeks after the last cycle of intraperitoneal irinotecan (75 mg) with concomitant palliative systemic therapy. With the exception of peripheral neuropathy, which will be reported indefinitely, ranging from CTCAE grade 1-5.
Patient-reported outcomes (PROs) with EQ-5D-5L
Assessed with the 5-level EQ-5D by EuroQol group (EQ-5D-5L) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
Patient-reported outcomes (PROs) with EORTC QLQ-C30
Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EORTC QLQ-C30 comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales, three symptom scales and one global health status scale. The remaining six single-item assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Patient-reported outcomes (PROs) with EORTC QLQ-CR29
Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire, specifically for colorectal cancer (EORTC QLQ-CR29) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The resulting QLQ-CR29 consisted of four scales and 19 individual items. Higher scores indicate a higher level of symptoms (i.e. a worse state of the patient).
Healthcare costs
According to the Dutch manual for cost analysis in health care research, and assessed with the iMTA Medical Consumption Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The volumes of used healthcare costs were multiplied with the unit costs of these corresponding services.
Productivity loss costs.
Assessed with the iMTA Productivity Cost Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Occurrence and degree of nephrotoxicity
Assessed during standard-of-care laboratory assessment for nephrotoxicity (creatinine, eGFR, and ureum) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Occurrence and degree of hepatotoxicity
Assessed during standard-of-care laboratory assessment for hepatotoxicity (albumin, bilirubin, AST, ALT, LD, AF, yGT) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Occurrence and degree of haematological toxicity
Assessed during standard-of-care laboratory assessment for haematological toxicity (haemoglobin, leucocytes, thrombocyte) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Response of Tumor marker during treatment
Assessed by carcino-embryonic antigen (CEA) analysis during standard laboratory analysis before each subsequent cycle
Number of patients that completed twelve cycles
To determine the number of patients completing twelve cycles of treatment with intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy, required dose reductions, and reasons for discontinuation.
Objective radiological response
assessed by thoracoabdominal CT at baseline, after the fourth cycle, after the eighth cycle, and after the twelfth cycle according to RECIST.
Peritoneum/plasma ratio of intraperitoneal irinotecan
To determine the the peritoneum/plasma ratio of intraperitoneal during the first and fourth cycle of intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy. Whole blood and peritoneal fluid will be drawn from a peripheral intravenous access and the peritoneal access port, respectively, and collected in 3 mL lithium heparin tubes and 2 mL cryotubes, respectively, at the following moments after the start of irinotecan infusion; t=0, at the end of infusion (EOI), t=30 minutes after EOI and t =2 hrs after EOI and t = 4hrs after EOI. The ratio between the Area Under the Curve (AUC) between irinotecan measured in the peritoneum and measured in the plasma is taken.
Full Information
NCT ID
NCT06003998
First Posted
November 8, 2022
Last Updated
August 15, 2023
Sponsor
Catharina Ziekenhuis Eindhoven
1. Study Identification
Unique Protocol Identification Number
NCT06003998
Brief Title
Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab
Acronym
INTERACT-II
Official Title
Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab for Patients With Unresectable Colorectal Peritoneal Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 27, 2022 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catharina Ziekenhuis Eindhoven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The rationale of the current study is that the addition of intraperitoneal irinotecan (75 mg) to palliative systemic therapy is feasible and safe, and might result in an increased overall and progression free survival in patients with unresectable colorectal peritoneal metastases. The primary objectives are to explore the overall survival for the addition of intraperitoneal irinotecan (75 mg) to palliative systemic therapy in patients with unresectable colorectal peritoneal metastases. Secondary objectives are to assess the progression-free survival, toxicity profile, patient reported outcomes, costs, tumor response during trial treatment, and the systemic and intraperitoneal pharmacokinetics of irinotecan and SN-38. This is a single-arm, open-label, phase II study and patients will receive intraperitoneal irinotecan (75 mg) in combination with modified FOLFOX4 + bevacizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Peritoneal Metastases
Keywords
Peritoneal metastases, colorectal cancer, Intraperitoneal, Irinotecan
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
85 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intraperitoneal irinotecan 75 mg + mFOLFOX-4 and bevacizumab
Arm Type
Experimental
Arm Description
Intraperitoneal irinotecan, 75 mg flat dose + systemic oxaliplatin, 5-Fluorouracil and bevacizumab (mFOLFOX+beva) (dose via standard of care)
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Intraperitoneal irinotecan
Intervention Description
2 weekly IP irinotecan (max 12 cycles), dose 75 mg flat dose
Intervention Type
Drug
Intervention Name(s)
FOLFOX regimen
Other Intervention Name(s)
5-FU + oxaliplatin
Intervention Description
FOLFOX-4 regimens consist of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46-h infusion
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab according to standard of care
Primary Outcome Measure Information:
Title
Overall survival
Description
calculated from (a) the interval from diagnosis of peritoneal metastases until death or last follow-up; (b) the interval from the first day of the first cycle until death or last follow-up).
Time Frame
3 year
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
calculated from the interval from the start of trial treatment until first evidence of intraperitoneal and/or systemic disease progression, and/or start of second-line systemic therapy, or last follow-up
Time Frame
3 year
Title
Toxicity in CTCAE grading
Description
Defined as the number of patients who experience / the total number of Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) grade 3-5 adverse events, measured up to four weeks after the last cycle of intraperitoneal irinotecan (75 mg) with concomitant palliative systemic therapy. With the exception of peripheral neuropathy, which will be reported indefinitely, ranging from CTCAE grade 1-5.
Time Frame
28 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Toxicity measured up to four weeks after last cycle.
Title
Patient-reported outcomes (PROs) with EQ-5D-5L
Description
Assessed with the 5-level EQ-5D by EuroQol group (EQ-5D-5L) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Title
Patient-reported outcomes (PROs) with EORTC QLQ-C30
Description
Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EORTC QLQ-C30 comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales, three symptom scales and one global health status scale. The remaining six single-item assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Title
Patient-reported outcomes (PROs) with EORTC QLQ-CR29
Description
Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire, specifically for colorectal cancer (EORTC QLQ-CR29) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The resulting QLQ-CR29 consisted of four scales and 19 individual items. Higher scores indicate a higher level of symptoms (i.e. a worse state of the patient).
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Title
Healthcare costs
Description
According to the Dutch manual for cost analysis in health care research, and assessed with the iMTA Medical Consumption Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The volumes of used healthcare costs were multiplied with the unit costs of these corresponding services.
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Title
Productivity loss costs.
Description
Assessed with the iMTA Productivity Cost Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.
Title
Occurrence and degree of nephrotoxicity
Description
Assessed during standard-of-care laboratory assessment for nephrotoxicity (creatinine, eGFR, and ureum) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
Title
Occurrence and degree of hepatotoxicity
Description
Assessed during standard-of-care laboratory assessment for hepatotoxicity (albumin, bilirubin, AST, ALT, LD, AF, yGT) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
Title
Occurrence and degree of haematological toxicity
Description
Assessed during standard-of-care laboratory assessment for haematological toxicity (haemoglobin, leucocytes, thrombocyte) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
Title
Response of Tumor marker during treatment
Description
Assessed by carcino-embryonic antigen (CEA) analysis during standard laboratory analysis before each subsequent cycle
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
Title
Number of patients that completed twelve cycles
Description
To determine the number of patients completing twelve cycles of treatment with intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy, required dose reductions, and reasons for discontinuation.
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles.
Title
Objective radiological response
Description
assessed by thoracoabdominal CT at baseline, after the fourth cycle, after the eighth cycle, and after the twelfth cycle according to RECIST.
Time Frame
24 weeks. Each cycle is 2 weeks, maximum of 12 cycles. Measured at baseline, after the fourth cycle, after the eighth cycle, and after the twelfth cycle.
Title
Peritoneum/plasma ratio of intraperitoneal irinotecan
Description
To determine the the peritoneum/plasma ratio of intraperitoneal during the first and fourth cycle of intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy. Whole blood and peritoneal fluid will be drawn from a peripheral intravenous access and the peritoneal access port, respectively, and collected in 3 mL lithium heparin tubes and 2 mL cryotubes, respectively, at the following moments after the start of irinotecan infusion; t=0, at the end of infusion (EOI), t=30 minutes after EOI and t =2 hrs after EOI and t = 4hrs after EOI. The ratio between the Area Under the Curve (AUC) between irinotecan measured in the peritoneum and measured in the plasma is taken.
Time Frame
8 weeks. Each cycles is 2 weeks. Measured during cycle 1 and cycle 4.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed colorectal cancer;
Radiologically and clinically or pathologically confirmed unresectable colorectal peritoneal metastases (e.g. PCI >20, extensive small bowel involvement, unresectable disease due to anatomical location);
WHO performance score of 0-1 with a life expectancy of >3 months;
Aged 18 years or older;
Written informed consent;
Exclusion Criteria:
Presence of extensive systemic metastases that are deemed to be the dominant factor determining prognosis in terms of life expectancy and performance status [e.g. no imminent threat of impaired organ functioning due to the presence of systemic metastases]);
Prior cytoreductive surgery;
Prior palliative systemic therapy for colorectal cancer;
Prior neo-adjuvant/adjuvant systemic therapy for colorectal cancer within the last 6 months;
Homozygous UGT1A1*28 genotype;
Homozygous dihydropyrimidine dehydrogenase (DPD) deficiency
Microsatellite instable (MSI) primary tumor
Any contra-indication for the planned chemotherapy (e.g. active infection, serious concomitant disease, severe allergy), as determined by the medical oncologist;
Inadequate organ functions, defined as an haemoglobin of <5 mmol/L, an absolute neutrophil count of <1.5 x 109/L, platelet count of <100 x 109/L, serum creatinine of >1.5 x ULN, creatinine clearance of <30 ml/min, Bilirubin > 2x ULN and liver transaminases of >5 x ULN.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pim Burger, MD, PhD
Phone
0031402397150
Email
pim.burger@catharinaziekenhuis.nl
Facility Information:
Facility Name
Catharina Hospital
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teun van den Heuvel, MD
Phone
0031 40 239 6351
Email
teun.vd.heuvel@catharinaziekenhuis.nl
Facility Name
Erasmus Medical Centre
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Niels Guchelaar
Phone
0031 10 703 9640
Email
n.guchelaar@erasmusmc.nl
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intraperitoneal Irinotecan With Concomitant FOLFOX and Bevacizumab
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