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

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective as the same regimen given continuously, in unresectable metastatic RAS and BRAF wild type colorectal cancer patients. Correlative studies on tumor and blood samples could identify potential biomarkers of efficacy and help defining personalized treatment strategy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute, Naples
• Treatments: Fluorouracil; Folic Acid; Irinotecan; Leucovorin; Levoleucovorin; Panitumumab

Criteria

Inclusion Criteria:

1. Written informed consent to study procedures and to molecular analyses;

2. Histologically proven diagnosis of colorectal cancer with wildtype RAS and BRAF status in certified laboratories;

3. Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;

4. At least one measurable lesion according to RECIST1.1 criteria;

5. Availability of a tumor sample (primary and/or metastatic sites) for exploratory research;

6. Age ≥ 18 years;

7. ECOG PS ≤ 2;

8. Life expectancy of at least 12 weeks;

9. Previous adjuvant chemotherapy allowed only if more than 6 months elapsed between the end of adjuvant and first relapse;

10. Neutrophils ≥ 1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl;

11. Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or < 5 x UNL in case of liver metastases) alkaline phosphatase ≤ 2.5 x UNL (or < 5 x UNL in case of liver metastases);

12. Creatinine clearance ≥50 mL/min or serum creatinine ≤ 1.5 x UNL;

13. Female with a childbearing potential and male subjects must be willing to use adequate contraception (barrier contraceptive measure, oral contraception, intrauterine device);

14. Will and ability to comply with the protocol.

Exclusion Criteria:

1. Previous treatment for metastatic disease;

2. Radiotherapy to any site within 4 weeks before the study;

3. Any contraindication to use Panitumumab, Irinotecan, 5-FU or folinic acid

4. Known or clinically suspected brain metastases.

5. History or evidence upon physical examination of CNS disease unless adequately treated.

6. Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.

7. Diagnosis of interstitial pneumonitis or pulmonary fibrosis;

8. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration or which, in the investigating physician's opinion, rules out the patient's participation in the study;

9. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication;

10. Treatment with any investigational drug within 30 days prior to enrolment;

11. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;

12. Lack of physical integrity of the gastrointestinal tract or history of acute or sub-acute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.

13. Disease that is deemed potentially resectable.

14. Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.

15. Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.

16. Breastfeeding

17. 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.