Intermittent or Continuous Panitumumab Plus FOLFIRI for Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer

Phase 3

Recruiting

• Conditions: Colorectal Cancer Stage IV
• Interventions: Drug: Panitumumab; Drug: Irinotecan; Drug: 5-fluorouracil; Drug: L-folinic acid

• Registration Number: NCT06509126
• Lead Sponsor: National Cancer Institute, Naples

Brief Summary

The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective in first line as the same regimen given continuously, resulting in a Time to Treatment Failure (TTF) not inferior to that obtained with standard continuous regimen of Panitumumab plus FOLFIRI, in the treatment of metastatic left sided RAS/B-RAF wild-type colorect...

Detailed Description

This study is a multicentric open label academic randomized phase-3 study. The study population will include untreated and unresectable left sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients, eligible for first-line treatment. A total of 500 patients, 250 for arm, will be enrolled.
...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Status Verified: 2024-06
• Study Start: 2024-06-12
• Study First Submitted: 2024-06-14
• Study First Submitted QC: 2024-07-11
• Last Update Submitted: 2024-07-11
• Study First Posted: 2024-07-19
• Last Update Posted: 2024-07-19
• Primary Completion: 2028-01
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. Written informed consent to study procedures and to correlative studies.
2. Histologically proven left sided mCRC.
3. RAS/BRAF wild-type and pMMR and/or MSS status assessed at local centers according a validated method defined by EMA
4. Disease judged unresectable by the local multidisciplinary team
5. Patient candidate to receive Induction treatment with FOLFIRI plus panitumumab as per standard clinical practice
6. No prior treatments (chemotherapy, radiation or surgery) for mCRC. Surgery for primary CRC tumor before starting treatment is allowed.
7. Either sex aged ≥ 18
8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.
9. Imaging-documented measurable disease, according to RECIST 1.1 criteria.
10. Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory
11. Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL.
12. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN.
13. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula).
14. Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range

Read More

Exclusion Criteria

1. Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
2. Prior chemotherapy or any other medical treatment for mCRC (previous adjuvant chemotherapy is allowed if terminated > 6 months previously).
3. Major surgical intervention within 4 weeks prior to enrollment.
4. Pregnancy and breast-feeding.
5. Any brain metastases.
6. Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD) or known UGT1A1 homozygosity.
7. Required dose reduction of 5-fluorouracil in the past for toxicity.
8. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study.
9. History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form.
10. Participation in any interventional drug or medical device study within 30 days prior to treatment start.
11. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
12. History of interstitial pneumonitis or pulmonary fibrosis.
13. History of corneal perforation or ulceration keratitis

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INTERMITTENT ARM	Irinotecan	Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.
INTERMITTENT ARM	5-fluorouracil	Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.
CONTINUOUS ARM	Panitumumab	Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal
CONTINUOUS ARM	Irinotecan	Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal
CONTINUOUS ARM	5-fluorouracil	Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal
CONTINUOUS ARM	L-folinic acid	Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal
INTERMITTENT ARM	Panitumumab	Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.
INTERMITTENT ARM	L-folinic acid	Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.

Primary Outcome Measures

Name	Time	Method
Time to Treatment Failure	up to 1 year last patients randomized	Time to treatment failure (TTF) is defined as the time from randomization to the objective disease progression by RECIST 1.1 criteria occurred during the treatment (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first, or a treatment delay \> 28 days for toxicity

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to 1 year last patients randomized	(OS) is calculated as the time from randomization until the date of death from any cause.

Trial Locations

Locations (1)

Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale; 🇮🇹 Napoli, Italy