Actively Recruiting
Randomized Phase 3 Study of Intermittent or Continuous Panitumumab Plus FOLFIRI for First-line Treatment of Patients With Unresectable Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer (IMPROVE-2 Trial)
Led by National Cancer Institute, Naples · Updated on 2024-07-19
500
Participants Needed
1
Research Sites
21 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating two treatment approaches for patients with unresectable left sided RAS/BRAF wild-type metastatic colorectal cancer who have not received prior therapy for their metastatic disease. The study aims to determine if an intermittent first-line treatment with Panitumumab plus FOLFIRI chemotherapy is not worse than the standard continuous regimen in terms of time to treatment failure. The trial also includes correlative studies on tissue and blood samples to explore potential biomarkers and better understand tumor response and evolution during treatment. Participants will receive an induction phase of Panitumumab given intravenously every two weeks at 6 mg/kg combined with FOLFIRI chemotherapy. After induction, patients without disease progression are randomly assigned to either a continuous treatment arm, where Panitumumab plus FOLFIRI is given every two weeks until treatment failure or unacceptable toxicity, or an intermittent arm where treatment cycles are alternated with treatment-free intervals until disease progression. Tumor assessments by CT scan or MRI and blood marker tests occur every 8 weeks during treatment. Throughout the study, patients will undergo regular monitoring including imaging, laboratory tests, and quality of life questionnaires completed every 8 weeks until disease progression or study withdrawal. Safety is closely followed using standard criteria for adverse events. Biomarker analysis will be performed on tumor tissue and blood samples collected at baseline, during treatment, and at progression to correlate with patient outcomes. The primary outcome measure is time to treatment failure assessed up to one year after the last patient is randomized.
CONDITIONS
Brief Title
Intermittent or Continuous Panitumumab Plus FOLFIRI for Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Written informed consent to study procedures and correlative studies
- Histologically confirmed left sided metastatic colorectal cancer
- RAS/BRAF wild-type and pMMR and/or MSS status confirmed by validated local testing
- Disease considered unresectable by multidisciplinary team
- Candidate for induction treatment with FOLFIRI plus panitumumab
- No prior treatment for metastatic colorectal cancer; prior surgery for primary tumor allowed
- Age 18 years or older
- ECOG Performance Status of 0 or 1
- Measurable disease per RECIST 1.1 criteria
- Known dihydropyrimidine dehydrogenase (DPYD) activity; UGT1A1 polymorphism analysis recommended
- Adequate bone marrow function with ANC ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, hemoglobin ≥ 9 g/dL
- Adequate liver function with bilirubin ≤ 1.5 x ULN or ≤ 2 x ULN if biliary stent; AST/ALT ≤ 5 x ULN
- Adequate renal function with serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min (males) or ≥ 50 mL/min (females)
- Electrolytes within normal laboratory range
You will not qualify if you...
- Prior malignancy within 5 years except certain skin cancers or in situ cervical cancer
- Prior chemotherapy or other treatment for metastatic colorectal cancer (adjuvant chemo allowed if ended >6 months ago)
- Major surgery within 4 weeks before enrollment
- Pregnancy or breastfeeding
- Presence of brain metastases
- Complete DPYD deficiency or known UGT1A1 homozygosity
- Previous dose reduction of 5-fluorouracil due to toxicity
- Severe or uncontrolled systemic disease or conditions interfering with study compliance
- History of poor cooperation or inability to understand informed consent
- Participation in another interventional drug or device study within 30 days
- Sexually active patients not willing to use contraception during and 6 months after trial
- History of interstitial pneumonitis or pulmonary fibrosis
- History of corneal perforation or ulcerative keratitis
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months or until treatment failure or unacceptable toxicity
Participants receive induction treatment with Panitumumab plus FOLFIRI chemotherapy every two weeks for up to 8 cycles or until progressive disease, unacceptable toxicity, or withdrawal. After induction, participants are randomized to either continuous treatment until treatment failure or intermittent treatment cycles with treatment-free intervals until disease progression.
Biweekly visits for treatment administration; tumor assessments every 8 weeks
Duration - Up to 1 year after last treatment
Participants discontinuing treatment without progression will have tumor assessments every 8 weeks until disease progression or study withdrawal. Toxicity evaluations continue up to 4 weeks after the last treatment cycle. Quality of life questionnaires are completed every 8 weeks until progression, treatment failure, or death.
Tumor assessments every 8 weeks; periodic clinical visits for toxicity and quality of life assessments
Trial Site Locations
Total: 1 location
1
Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale
Naples, Italy, 80131
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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