Description:
The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results
in a prolonged progression free survival compared to cisplatin-pemetrexed as first line
treatment in patients with KRAS mutated non-small cell lung cancer.
Title
- Brief Title: Cisplatin-Pemetrexed Compared With Carboplatin-Paclitaxel-Bevacizumab in KRAS Mutated Non-small Cell Lung Cancer
- Official Title: Chemotherapy in KRAS Mutated Chemotherapy Naive Non-small Cell Lung Cancer Patients: a Phase III Study Comparing Cisplatin-pemetrexed With Carboplatin-paclitaxel-bevacizumab: NVALT 22
Clinical Trial IDs
- ORG STUDY ID:
NVALT 22
- NCT ID:
NCT02743923
Conditions
- Carcinoma, Non-Small Cell Lung
Interventions
Drug | Synonyms | Arms |
---|
carboplatin | | carboplatin-paclitaxel- bevacizumab |
paclitaxel | | carboplatin-paclitaxel- bevacizumab |
Bevacizumab | | carboplatin-paclitaxel- bevacizumab |
Pemetrexed | | cisplatin-pemetrexed |
cisplatin | | cisplatin-pemetrexed |
Purpose
The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results
in a prolonged progression free survival compared to cisplatin-pemetrexed as first line
treatment in patients with KRAS mutated non-small cell lung cancer.
Detailed Description
KRAS mutations occur in 30% of patients with non-small cell lung cancer, especially
adenocarcinoma. For long time KRAS mutation has been related with poor prognosis and poor
response to chemotherapy. Recent data however show that this is both not true. It seems that
response, progression free survival and overall survival is similar in KRAS mutated. Until
now no specific targeted therapy is available for KRAS mutated NSCLC patients. Optimization
of treatment in advanced NSCLC patients with a KRAS mutation could also be achieved by
selecting the best available chemotherapy treatment.
Two standard chemotherapy schemes are frequently used and FDA and EMA approved as first line
treatment for patients with adenocarcinoma: cisplatin-pemetrexed and
carboplatin-paclitaxel-bevacizumab.
The aim of this randomized phase III study is to compare two standard treatment regimens in
patients with KRAS mutated, advanced stage NSCLC and the hypothesis is that bevacizumab with
chemotherapy improves outcomes compared to chemotherapy alone as first line treatment.
Furthermore the outcome for the different KRAS mutations will be studied.
Treatment with one of the two following chemotherapy combinations according to the label:
carboplatin-paclitaxel-bevacizumab or cisplatin-pemetrexed q3wks for up to six cycles.
Continuation maintenance with bevacizumab and pemetrexed is allowed until progression. Blood
and archival tissue will be optionally collected for translational research. This may help to
identify subgroups of patients who are likely better treated with a specific treatment
regimen.
Trial Arms
Name | Type | Description | Interventions |
---|
carboplatin-paclitaxel- bevacizumab | Active Comparator | carboplatin AUC 6, paclitaxel 200 mg/m2, bevacizumab 15 mg/kg all administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by bevacizumab maintenance every 3 weeks until progression | - carboplatin
- paclitaxel
- Bevacizumab
|
cisplatin-pemetrexed | Active Comparator | pemetrexed 500 mg/m2 administered intravenously on day 1 and cisplatin 75 mg/m2 administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by maintenance pemetrexed every 3 weeks until progression. | |
Eligibility Criteria
Inclusion Criteria:
1. Histologically or cytologically confirmed (non-squamous) NSCLC incurable locally
advanced or metastatic (stage IIIB and stage IV) disease.
2. Documented KRAS mutation
3. Chemotherapy-naive NSCLC patients. Adjuvant chemotherapy or chemoradiotherapy is
allowed when given > 1 year for study entry. Previous anti-PD(L1) therapy for advanced
disease is allowed.
4. At least one unidimensionally measurable lesion meeting RECIST1.1.
5. ECOG PS 0-2
6. Age ≥ 18 years
7. Adequate organ function, including:
- Adequate bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
- Hepatic: bilirubin ≤1.5 x ULN, AP, ALT, AST ≤ 3.0 x ULN AP, ALT, and AST ≤5 xULN
is acceptable if the liver has tumor involvement
- Renal: calculated creatinine clearance ≥ 60 ml/min based on the Cockroft-Gault
formula.
- Urine protein (dip-stick) < 2 +; when ≥ 2 +: 24 hours urine protein ≤ 1 gr.
8. Signed informed consent
9. Male and female patients with reproductive potential must use an approved
contraceptive method, if appropriate. Female patients with childbearing potential must
have a negative serum pregnancy test within 7 days prior to study enrollment.
Exclusion Criteria:
1. Pregnant or lactating women
2. Clinically significant (i.e. active) cardiovascular disease: congestive heart failure
>NYHA class 2; CVA or myocardial infarction < 6 months prior to study entry;
uncontrolled hypertension (blood pressure systolic > 150 mmHg and/or diastolic > 100
mmHg)
3. History of hemoptysis ≥ grade 2 (bright red blood of at least 2,5 ml in the last 3
months)
4. Evidence of tumor invading major blood vessels on imaging (i.e. superior vena cava or
pulmonary artery)
5. Patients with evidence or history of bleeding diathesis
6. Non-healing wound or ulcer
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | progression free survival |
Time Frame: | Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | disease control rate |
Time Frame: | Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months. |
Safety Issue: | |
Description: | |
Measure: | overall survival |
Time Frame: | date of randomization to the date of death from any cause, assessed up to 60 months. |
Safety Issue: | |
Description: | Stratification for KRAS mutation (G12V versus G12C versus other) |
Measure: | outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets). |
Time Frame: | date of randomization to the date of death from any cause, assessed up to 60 months. |
Safety Issue: | |
Description: | The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. Subgroup analyses are planned to explore treatment effect in these different KRAS mutations groups. At baseline the metastatic patterns of these subgroups will be described. KRAS mutations in NSCLC occur mainly in codon 12 and 13.
Stratification for KRAS mutation (G12V versus G12C versus other) at randomization. |
Measure: | response by Crabb criteria (if applicable) |
Time Frame: | Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | The Netherlands Cancer Institute |
Last Updated
August 28, 2020