Metastatic Colorectal Cancer
Conditions
Keywords
metastatic colorectal cancer, maintenance therapy, Panitumumab, Vectibix®
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.
Interventions
DRUGPanitumumab (Within maintenance phase)
DRUGmFOLFOX6 (Within re-induction phase)
DRUGPanitumumab (Within re-induction phase)
Sponsors
ClinAssess GmbH
Amgen
AIO-Studien-gGmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| failure of treatment strategy | Until end of follow up (24 months after randomization) | Time from randomization until failure (death/ progression) of treatment strategy |
| Safety | Until end of follow-up (24 months after randomization) | Overall safety |
| Health and skin related Quality of life | Until end of follow-up (24 months after randomization) | Health and skin related Quality of life |
| Overall survival | Until end of follow-up (24 months after randomization) | Overall survival measured from time of randomization and from time of registration |
Countries
Germany
Outcome results
None listed