Maintenance Therapy With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction and Re-induction After Progress for 1st-line Treatment of Metastatic Colorectal Cancer

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Maintenance Chemotherapy; Drug: Panitumumab (Within maintenance phase); Drug: Panitumumab (Within re-induction phase); Drug: mFOLFOX6 (Within re-induction phase)

• Registration Number: NCT01991873
• Lead Sponsor: AIO-Studien-gGmbH

Brief Summary

This is a phase II, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy.

Eligible patients will be treated within a 12-week induction therapy. Those patients achieving CR/PR or SD at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. In case of progression, re-induction treatment will be started.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-10-22
• Study First Submitted QC: 2013-11-18
• Study First Posted: 2013-11-25
• Study Start: 2014-04
• Primary Completion: 2023-02-18
• Study Completion: 2023-02-18
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-13
• Last Update Posted: 2023-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 387

Inclusion Criteria

• Signed written informed consent

• Male or female ≥ 18 years of age

• Histologically proven metastatic colorectal cancer

• Molecular testing showing RAS wild-type in colorectal carcinoma cells

• Life expectancy > 12 weeks

• At least one measurable lesion according to RECIST 1.1

• Adequate bone marrow, liver, kidney, organ and metabolic function

• Bone marrow function:

  • leukocyte count ≥ 3.0 × 109/L
  • ANC ≥ 1.5 × 109/L
  • platelet count ≥ 100 × 109/L
  • hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level)

• Hepatic function:

  • Total bilirubin ≤ 1.5 × UNL
  • ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)
  • AP ≤ 5 × UNL

• Renal function:

  • Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL

• Metabolic function:

  • Magnesium ≥ lower limit of normal
  • Calcium ≥ lower limit of normal

• ECOG performance status 0 - 1

• Women of child-bearing potential must have a negative pregnancy test

Exclusion Criteria

• Previous treatment for colorectal cancer in the metastatic setting

• Previous EGFR-targeting therapy < 6 months after end of adjuvant therapy

• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids

• Chronic inflammatory bowel disease

• Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2

• Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up

• Significant disease that, in the investigator's opinion, would exclude the patient from the study

• History of cardiac disease; defined as:

  • Congestive heart failure > New York Heart Association (NYHA) class 2
  • Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed)
  • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
  • Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)

• Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan

• Known HIV, hepatitis B or C infection

• Known hypersensitivity reaction to any of the study components

• Radiotherapy, major surgery or any investigational drug 30 days before registration

• Pregnancy or lactation or planning to be pregnant during treatment and within 6 months after the end of treatment

• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 6 months after the end of treatment

• Known alcohol or drug abuse

• Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Maintenance Chemotherapy + Panitumumab	Panitumumab (Within maintenance phase)	Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy w/o Panitumumab	Panitumumab (Within re-induction phase)	Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy + Panitumumab	Maintenance Chemotherapy	Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy + Panitumumab	mFOLFOX6 (Within re-induction phase)	Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy + Panitumumab	Panitumumab (Within re-induction phase)	Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy w/o Panitumumab	Maintenance Chemotherapy	Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15
Maintenance Chemotherapy w/o Panitumumab	mFOLFOX6 (Within re-induction phase)	Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Until end of follow-up (24 months after randomization)	Progression-free survival during maintenance therapy defined as time from randomization until disease progression or death, whatever occurs first.

Secondary Outcome Measures

Name	Time	Method
Health and skin related Quality of life	Until end of follow-up (24 months after randomization)	Health and skin related Quality of life
failure of treatment strategy	Until end of follow up (24 months after randomization)	Time from randomization until failure (death/ progression) of treatment strategy
Progression-free survival of re-induction	From start of re-induction therapy until progress or end of follow-up (24 months after randomization)	Progression-free survival during re-induction therapy
Objective response after 12 weeks of induction chemotherapy	12 weeks after start of induction chemotherapy	Objective response after 12 weeks of induction chemotherapy
Objective best response during maintenance and re-induction	Start of maintenance- until end of re-inductin therapy (expected average of 8 months)	Objective best response during maintenance and re-induction
Overall survival	Until end of follow-up (24 months after randomization)	Overall survival measured from time of randomization and from time of registration
Safety	Until end of follow-up (24 months after randomization)	Overall safety

Trial Locations

Locations (2)

St.-Antonius-Hospital Eschweiler; 🇩🇪 Eschweiler, Germany

Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven; 🇩🇪 Wilhelmshaven, Germany