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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02743923
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Last Update Posted : December 21, 2021
Sponsor:
Collaborator:
Dutch Society of Physicians for Pulmonology and Tuberculosis
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small Cell Lung Drug: carboplatin Drug: paclitaxel Drug: Bevacizumab Drug: Pemetrexed Drug: cisplatin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 2016
Actual Primary Completion Date : September 19, 2021
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: carboplatin-paclitaxel- bevacizumab
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
Drug: carboplatin
AUC 6

Drug: paclitaxel
200mg/m2

Drug: Bevacizumab
15 mg/kg

Active Comparator: cisplatin-pemetrexed
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.
Drug: Pemetrexed
500 mg/m2

Drug: cisplatin
75 mg/m2




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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. ]
  2. overall survival [ Time Frame: date of randomization to the date of death from any cause, assessed up to 60 months. ]
    Stratification for KRAS mutation (G12V versus G12C versus other)

  3. 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. ]

    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.


  4. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743923


Locations
Show Show 28 study locations
Sponsors and Collaborators
The Netherlands Cancer Institute
Dutch Society of Physicians for Pulmonology and Tuberculosis
Investigators
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Principal Investigator: Anne-Marie C Dingemans, MD PhD Dutch Society of Physicians for Pulmonology and Tuberculosis
Additional Information:
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02743923    
Other Study ID Numbers: NVALT 22
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: December 21, 2021
Last Verified: December 2021
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Bevacizumab
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors