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

NCT ID: NCT02743923

Last Updated: 2021-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

203 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2024-04-30

Brief Summary

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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

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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.

Conditions

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Carcinoma, Non-Small Cell Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

carboplatin

Intervention Type DRUG

AUC 6

paclitaxel

Intervention Type DRUG

200mg/m2

Bevacizumab

Intervention Type DRUG

15 mg/kg

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.

Group Type ACTIVE_COMPARATOR

Pemetrexed

Intervention Type DRUG

500 mg/m2

cisplatin

Intervention Type DRUG

75 mg/m2

Interventions

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carboplatin

AUC 6

Intervention Type DRUG

paclitaxel

200mg/m2

Intervention Type DRUG

Bevacizumab

15 mg/kg

Intervention Type DRUG

Pemetrexed

500 mg/m2

Intervention Type DRUG

cisplatin

75 mg/m2

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Society of Physicians for Pulmonology and Tuberculosis

OTHER

Sponsor Role collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anne-Marie C Dingemans, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Dutch Society of Physicians for Pulmonology and Tuberculosis

Locations

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VUmc Medical Center

Amsterdam, North Holland, Netherlands

Site Status

Medical spectrum Twente

Enschede, Overijssel, Netherlands

Site Status

Meander Medical Center

Amersfoort, Utrecht, Netherlands

Site Status

Jeroen Bosch Hospital

's-Hertogenbosch, , Netherlands

Site Status

ZGT

Almelo, , Netherlands

Site Status

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status

OLVG

Amsterdam, , Netherlands

Site Status

Gelre Ziekenhuis

Apeldoorn, , Netherlands

Site Status

Amphia Hospital

Breda, , Netherlands

Site Status

Deventer Ziekenhuis

Deventer, , Netherlands

Site Status

Albert Schweitzer ziekenhuis

Dordrecht, , Netherlands

Site Status

Ziekenhuis Gelderse Vallei

Ede, , Netherlands

Site Status

Maxima Medisch Centrum

Eindhoven, , Netherlands

Site Status

Groene Hart

Gouda, , Netherlands

Site Status

UMCG

Groningen, , Netherlands

Site Status

Martini Ziekenhuis

Groningen, , Netherlands

Site Status

Tergooi ziekenhuizen

Hilversum, , Netherlands

Site Status

Spaarne Gasthuis

Hoofddorp, , Netherlands

Site Status

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Maasstad ziekenhuis

Rotterdam, , Netherlands

Site Status

St. Fransicus Gasthuis

Rotterdam, , Netherlands

Site Status

Haga

The Hague, , Netherlands

Site Status

Medical Center Haaglanden

The Hague, , Netherlands

Site Status

Diakonessenhuis Utrecht

Utrecht, , Netherlands

Site Status

St. Antonius ziekenhuis

Utrecht, , Netherlands

Site Status

VieCuri Medisch Centrum voor Noord-Limburg

Venlo, , Netherlands

Site Status

Isala Klinieken

Zwolle, , Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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NVALT 22

Identifier Type: -

Identifier Source: org_study_id