CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen
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| ClinicalTrials.gov Identifier: NCT05312398 |
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Recruitment Status :
Recruiting
First Posted : April 5, 2022
Last Update Posted : April 5, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Colorectal Adenocarcinoma | Drug: Cetuximab Drug: FOLFIRI Drug: FOLFOX regimen Drug: Irinotecan | Phase 2 |
Based on dynamic and longitudinal liquid biopsy assessment of RAS/BRAF status, that will be prospectively performed before each line of treatment, mCRC patients will be treated with cetuximab in combination with chemotherapy throughout three lines of therapy, as follows: FOLFIRI plus cetuximab (first line); FOLFOX plus cetuximab (second line); irinotecan plus cetuximab (third line) in case of RAS/BRAF WT at each time point of progression. If at progression after the first line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with FOLFOX plus bevacizumab as the second line of therapy. If at progression after the second line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with regorafenib or trifluridine-tipiracil (investigator's choice), as third line of therapy. Each treatment will be administered using standard doses and schedules until progression of disease or unacceptable toxicity.
This study will also evaluate the activity and efficacy of cetuximab re-introduction in combination with irinotecan as third line therapy in the concept of re-challenge for those patients that will be treated in second line with FOLFOX plus bevacizumab, having a RAS or BRAF mutant disease at the time of progression after FOLFIRI plus cetuximab first line treatment. A novel characteristic of this program is that the therapeutic algorithm will be defined at each treatment decision (first line, second line and third line) in a prospective fashion in each patient by liquid biopsy assessment of RAS/BRAF status
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 200 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | 3 treatment lines in mCRC patients with RAS/BRAF wt tumors at start of first line. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio- Marker-driven Cetuximab-based Treatment Regimen Over 3 Treatment Lines in mCRC Patients With RAS/BRAF wt Tumors at Start of First Line |
| Actual Study Start Date : | July 15, 2021 |
| Estimated Primary Completion Date : | August 15, 2025 |
| Estimated Study Completion Date : | June 15, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: single arm
This is an open-label phase II study investigating the efficacy and safety of a bio-marker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wt tumors at start of first line. Based on dynamic and longitudinal liquid biopsy assessment of RAS/BRAF status, that will be prospectively performed before each line of treatment, mCRC patients will be treated with cetuximab in combination with chemotherapy throughout three lines of therapy, as follows:
If at progression after the first line or after the second line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with FOLFOX plus bevacizumab as second line of therapy, or with regorafenib or with trifluridine-tipiracil (investigator's choice) as third line therapy. |
Drug: Cetuximab
I LINE: - FOLFIRI + cetuximab FOLFIRI: 200 mg L-folinic acid with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days. Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter II LINE: - FOLFOX + cetuximab FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days. Cetuximab: as I line THIRD LINE: - Irinotecan + cetuximab Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line Other Name: Erbitux Drug: FOLFIRI I LINE: - FOLFIRI + cetuximab FOLFIRI: 200 mg L-folinic acid given concurrently with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days. Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter Drug: FOLFOX regimen II LINE: - FOLFOX + cetuximab FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days. Cetuximab: as I line Other Name: FOLFOX Drug: Irinotecan III LINE: - Irinotecan + cetuximab Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line |
- RR [ Time Frame: up to 59 months ]Response rate (RR) for each line of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in patients with RAS/BRAF wild type (WT) mCRCregimen over 3 treatment lines in patients with RAS/BRAF wild type (WT) mCRC at start of first line therapy
- PFS [ Time Frame: from 8 weeks to 59 months (from the start of therapy until the first observation of disease progression or death due to any cause) ]Progression free survival (PFS) for each line
- OS [ Time Frame: up to 59 months ]Overall Survival
- AE [ Time Frame: from screening up to 59 months ]Safety: Adverse events graded according NCI CTCAE v 5.0
- EORTC Core Quality of Life questionnaire EORTC QLQ C30 [ Time Frame: At screening, for each line of therapy at Week 4, at Week 25 of treatment start and at progression ]The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items
- DERMATOLOGY LIFE QUALITY INDEX (DLQI) [ Time Frame: at screening, for each line of therapy at Week 4, at Week 25 of treatment start and at progression ]The DLQI consists of 10 questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week.
- Explorative objective: RR for each line of therapy [ Time Frame: from screening up to 23 months ]the response rates for each line of therapy of RAS/BRAF WT mCRC patients who will be treated in a continuum of care strategy with cetuximab across all three therapy lines
- Exploratory objective: cumulative PFS [ Time Frame: from screening up to 23 months ]the cumulative progression free survivals of RAS/BRAF WT mCRC patients who will be treated in a continuum of care strategy with cetuximab across all three therapy lines
- Explorative objective: overall survival [ Time Frame: from screening up to 23 months ]overall survival of RAS/BRAF WT mCRC patients who will be treated in a continuum of care strategy with cetuximab across all three therapy lines
- Translational analyses using next generation sequencing (NGS) technologies [ Time Frame: At day 1 of each line of therapy ]
Molecular profiles of tumor tissue and liquid biopsy samples (somatic mutations identified in tumor tissue by next generation sequencing) and surrogate markers of treatment activity (changes in molecular profile of liquid biopsies). Translational analyses of tumor biomarkers will be performed
These include mutation in RAS, BRAF, PI3KCA; amplification of HER2, MET and loss of PTEN expression, all of which are implicated in resistance to anti-EGFR treatment.
Moreover, 324 genes NGS panels will provide information regarding potential predictive and prognostic biomarkers of colorectal cancer disease.
Fecal samples will be used for gut microbioma analysis, to understand how the composition of gut microbiome could influence treatment outcome and tolerability.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically proven diagnosis of colorectal adenocarcinoma
- Diagnosis of metastatic disease
- RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis
- Measurable disease according to Response Evaluation Criteria in Solid Tumors RECIST criteria, vers.1.1)
- Male or female patients ≥ 18 years of age
- ECOG Performance Status 0,1
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Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters:
Bone marrow:
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100 x 109/L
Liver function:
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (SGPT) ≤ 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN
Renal function:
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
- If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment
- If female and of childbearing potential, or if male, agreement to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 3 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate
- Signed informed consent obtained before screening.
Exclusion Criteria:
- Any contraindication to the use of cetuximab, Irinotecan, 5-FU, oxaliplatin, folinic acid,bevacizumab, trifluridine-tipiracil, regorafenib
- Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix
- Pregnancy (exclusion to be ascertained by a beta hCG test)
- Breastfeeding
- Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception•
- Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study, Grade III or IV heart failure (NYHA classification)
- Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
- Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
- Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study
- Known or clinically suspected brain metastases
- History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
- Severe, non-healing wounds, ulcers or bone fractures
- Uncontrolled hypertension
- Marked proteinuria (nephrotic syndrome)
- Known DPD deficiency (specific screening not required)
- Known history of alcohol or drug abuse
- A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study
- Absent or restricted legal capacity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05312398
| Contact: Fortunato Ciardiello | 0815666760 | fortunato.ciardiello@unicampania.it | |
| Contact: Giulia Martini | 0815666729 | giulia.martini@unicampania.it |
Show 25 study locations
| Principal Investigator: | Fortunato Ciardiello | A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli" |
| Responsible Party: | Fortunato Ciardiello, Principal Investigator, University of Campania "Luigi Vanvitelli" |
| ClinicalTrials.gov Identifier: | NCT05312398 |
| Other Study ID Numbers: |
CAPRI2-MS062202-0123 |
| First Posted: | April 5, 2022 Key Record Dates |
| Last Update Posted: | April 5, 2022 |
| Last Verified: | March 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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