Clinical Trials /

Cisplatin-Pemetrexed Compared With Carboplatin-Paclitaxel-Bevacizumab in KRAS Mutated Non-small Cell Lung Cancer

NCT02743923

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
carboplatincarboplatin-paclitaxel- bevacizumab
paclitaxelcarboplatin-paclitaxel- bevacizumab
Bevacizumabcarboplatin-paclitaxel- bevacizumab
Pemetrexedcisplatin-pemetrexed
cisplatincisplatin-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

NameTypeDescriptionInterventions
carboplatin-paclitaxel- bevacizumabActive Comparatorcarboplatin 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-pemetrexedActive Comparatorpemetrexed 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.
  • Pemetrexed
  • cisplatin

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

March 12, 2018