Clinical trial NCT01991873: 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
Official title: Randomized Phase II Study for Evaluation of Efficacy and Safety of Maintenance Treatment With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction Treatment With mFOLFOX6 Plus Panitumumab and Re-induction With mFOLFOX6 Plus Panitumumab in Case of Progression for First-line Treatment of Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
maintenance therapy
Panitumumab
Vectibix®
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
Collaborators: name: ClinAssess GmbH
name: Amgen
First posted: 2013-11-25
Enrollment: 387
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: Until end of follow-up (24 months after randomization)
Secondary outcomes:
measure: failure of treatment strategy
timeFrame: Until end of follow up (24 months after randomization)
measure: Progression-free survival of re-induction
timeFrame: From start of re-induction therapy until progress or end of follow-up (24 months after randomization)
measure: Objective response after 12 weeks of induction chemotherapy
timeFrame: 12 weeks after start of induction chemotherapy
measure: Objective best response during maintenance and re-induction
timeFrame: Start of maintenance- until end of re-inductin therapy (expected average of 8 months)
measure: Overall survival
timeFrame: Until end of follow-up (24 months after randomization)
measure: Safety
timeFrame: Until end of follow-up (24 months after randomization)
measure: Health and skin related Quality of life
timeFrame: Until end of follow-up (24 months after randomization)
Other outcomes:
Locations:
city: Eschweiler
country: Germany
facility: St.-Antonius-Hospital Eschweiler
city: Wilhelmshaven
country: Germany
facility: Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven
Study officials:
affiliation: Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven
name: Tanja Trarbach, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sommerhauser G, Kurreck A, Beck A, Fehrenbach U, Karthaus M, Fruehauf S, Graeven U, Mueller L, Koenig AO, V Weikersthal LF, Goekkurt E, Haas S, Stahler A, Heinemann V, Held S, Alig AHS, Kasper S, Stintzing S, Trarbach T, Modest DP. Depth of response of induction therapy and consecutive maintenance treatment in patients with RAS wild-type metastatic colorectal cancer: An analysis of the PanaMa trial (AIO KRK 0212). Eur J Cancer. 2023 Jan;178:37-48. doi: 10.1016/j.ejca.2022.09.011. Epub 2022 Oct 25.
citation: Modest DP, Karthaus M, Fruehauf S, Graeven U, Muller L, Konig AO, Fischer von Weikersthal L, Caca K, Kretzschmar A, Goekkurt E, Haas S, Kurreck A, Stahler A, Held S, Jarosch A, Horst D, Reinacher-Schick A, Kasper S, Heinemann V, Stintzing S, Trarbach T. Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212). J Clin Oncol. 2022 Jan 1;40(1):72-82. doi: 10.1200/JCO.21.01332. Epub 2021 Sep 17.