Study to Evaluate the Efficacy of FOLFOX + Panitumumab Followed by FOLFIRI + Bevacizumab (Sequence 1) Versus FOLFOX + Bevacizumab Followed by FOLFIRI + Panitumumab (Sequence 2) in Untreated Patients With Wild-type RAS Metastatic, Primary Left-sided, Unresectable Colorectal Cancer

NCT03635021 | Active Not Recruiting Phase 3

• 1 other identifier: TTD-18-01
• Study Type: interventional
• Target: 419
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the efficacy of FOLFOX + panitumumab followed by FOLFIRI + bevacizumab (Sequence 1) versus FOLFOX + bevacizumab followed by FOLFIRI + panitumumab (Sequence 2) in untreated patients with wild-type RAS metastatic, primary left-sided, unresectable colorectal cancer

Conditions

Colorectal Cancer

Keywords

colorectal cancer; FOLFOX; FOLFIRI; panitumumab; bevacizumab; wild-type RAS; primary left-sided

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate at 35 months

  35-month PFSR defined as the number of patients, who at 35 months after randomization, have not had second or first disease progression nor died (due to any cause), over the total number of evaluable patients.

  35 months after date of randomization

Secondary Outcomes (13)

• overall survival rate at 35 months

  35 months after date of randomization

• overall survival

  Baseline through the end of the study (up 72 months)

• progression-free from randomization to second progression or death

  Baseline through the end of the study (up 72 months)

• progression-free survival in first-line treatment and in second-line treatment

  Baseline through the end of the study (up 72 months)

• time to first-line treatment failure and to second-line treatment failure

  72 months

Other Outcomes (2)

• Impact of baseline biomarkers predictive of the efficacy

  Baseline through the end of the study (up 72 months)

• clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma

  Baseline through the end of the study (up 72 months)

Study Arms (2)

Sequence 1

EXPERIMENTAL

FOLFOX regimen panitumumab FOLFIRI regimen bevacizumab

Drug: FOLFOX regimen; Drug: Panitumumab; Drug: Bevacizumab; Drug: FOLFIRI regimen

Sequence 2

EXPERIMENTAL

FOLFOX regimen bevacizumab FOLFIRI regimen panitumumab

Drug: FOLFOX regimen; Drug: Panitumumab; Drug: Bevacizumab; Drug: FOLFIRI regimen

Interventions

FOLFOX regimen DRUG

oxaliplatin 85 mg/m2 administered by IV infusion over 120 minutes on Day 1, L-leucovorin 200 mg/m2 administered as a 2-hour IV infusion on Day 1 and 5-FU 400 mg/m2 administered as IV bolus over approximately 2 to 4 minutes on Day 1 followed by 5-FU 2400 mg/m2 administered as IV infusion over 46- 48 hours on Days 1 and 2

Sequence 1; Sequence 2

Panitumumab DRUG

6 mg/kg administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 14-day cycle

Sequence 1; Sequence 2

Bevacizumab DRUG

5 mg/kg administered by IV infusion over 60 minutes on Day 1 of each 14-day cycle

Sequence 1; Sequence 2

FOLFIRI regimen DRUG

irinotecan 180 mg/m2 administered as a 90 minutes IV infusion on Day 1, L-leucovorin 200 mg/m2 administered as a 2-hour IV infusion on Day 1 and 5-FU 400 mg/m2 administered as IV bolus over approximately 2 to 4 minutes on Day 1 followed by 5-FU 2400 mg/m2 administered as IV infusion over 46-48 hours on Days 1 and 2

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman at least 18 years old.
• Capable of understand, sign and date an informed consent approved by an IEC.
• Patients who had wild-type RAS status confirmed as per standard of care according to international guidelines prior to first-line initiation.
• \*RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117)
• At least one unidimensionally measurable lesion per RECIST criteria (version 1.1).
• ECOG performance status \< 2.
• Adequate bone marrow function: neutrophils ≥1.5 x109 / L; platelets ≥100 x109 /L; haemoglobin ≥ 9 g/dL.
• Hepatic, renal and metabolic function as follows:
• Total bilirubin count ≤1.5 x upper limit of normal (ULN), serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) and serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) ≤ 2.5 x ULN (5 x ULN for subjects with liver involvement of their cancer or 10 x ULN for subjects with bone involvement).
• Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥ 50 mL/min.

You may not qualify if:

• History of prior or concurrent central nervous system metastases.
• History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization.
• Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma.
• Prior adjuvant chemotherapy for colorectal cancer (stage I, II or III) terminated less than 6 month before metastatic disease was diagnosed.
• Prior use (as monotherapy or adjuvant treatment) of anti-EGFR antibody therapy (e.g. cetuximab), anti-VEGF or small molecule EGFR inhibitors (e.g. erlotinib).
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
• Uncontrolled hypertension.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography (CT).
• Treatment for systemic infection within 14 days before the start of study treatment.
• Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to NCI-CTCAE version 4.03).
• Clinically significant peripheral sensory neuropathy.
• Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment.
• History of Gilbert disease or known dihydropyrimidine deficiency syndrome.
• Recent (within 6 months before the start of study treatment) gastroduodenal ulcer to be active or uncontrolled.
• Recent (within 6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or other significant venous event.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Amgen: collaborator

Study Sites (1)

Spanish Cooperative Group for the Treatment of Digestive Tumors

Madrid, 28007, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folfox protocol; Panitumumab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ramón Salazar, MD, PhD

  Instituto Catalán de Oncología. Hospital Duran i Reynals

  STUDY CHAIR

• Alfredo Carrato, MD, PhD

  Hospital Universitario Ramon y Cajal

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 17, 2018
• Study Start: October 15, 2018
• Primary Completion: June 28, 2025
• Study Completion: June 28, 2025
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)