PanaMa: 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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Maintenance Chemotherapy + Panitumumab 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 |
Drug: Maintenance Chemotherapy
Other Names:
Drug: Panitumumab (Within maintenance phase)
Other Names:
Drug: mFOLFOX6 (Within re-induction phase)
Other Names:
Drug: Panitumumab (Within re-induction phase)
Other Names:
|
| Experimental: Maintenance Chemotherapy w/o Panitumumab 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 |
Drug: Maintenance Chemotherapy
Other Names:
Drug: mFOLFOX6 (Within re-induction phase)
Other Names:
Drug: Panitumumab (Within re-induction phase)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Health and skin related Quality of life [Until end of follow-up (24 months after randomization)]
Health and skin related Quality of life
Eligibility Criteria
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)
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Hepatic function:
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Total bilirubin ≤ 1.5 × UNL
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ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)
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AP ≤ 5 × UNL
-
Renal function:
-
Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL
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Metabolic function:
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Magnesium ≥ lower limit of normal
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Calcium ≥ lower limit of normal
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ECOG performance status 0 - 1
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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
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Chronic inflammatory bowel disease
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Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2
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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)
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Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
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Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)
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Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
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Known HIV, hepatitis B or C infection
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Known hypersensitivity reaction to any of the study components
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Radiotherapy, major surgery or any investigational drug 30 days before registration
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St.-Antonius-Hospital Eschweiler | Eschweiler | Germany | 52249 | |
| 2 | Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven | Wilhelmshaven | Germany | 26389 |
Sponsors and Collaborators
- AIO-Studien-gGmbH
- ClinAssess GmbH
- Amgen
Investigators
- Principal Investigator: Tanja Trarbach, Dr. med., Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- AIO-KRK-0212
- 2012-005422-30
- PanaMa_DE-2009-0003