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

NCT02743923 | Unknown Phase 3

• 1 other identifier: NVALT 22
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 28

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.

Conditions

Carcinoma, Non-Small Cell Lung

Outcome Measures

Primary Outcomes (1)

• progression free survival

  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 Outcomes (4)

• disease control rate

  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.

• overall survival

  date of randomization to the date of death from any cause, assessed up to 60 months.

• outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).

  date of randomization to the date of death from any cause, assessed up to 60 months.

• response by Crabb criteria (if applicable)

  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

Study Arms (2)

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

Drug: carboplatin; Drug: paclitaxel; Drug: 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.

Drug: Pemetrexed; Drug: cisplatin

Interventions

carboplatin DRUG

AUC 6

carboplatin-paclitaxel- bevacizumab

paclitaxel DRUG

200mg/m2

carboplatin-paclitaxel- bevacizumab

Bevacizumab DRUG

15 mg/kg

carboplatin-paclitaxel- bevacizumab

Pemetrexed DRUG

500 mg/m2

cisplatin-pemetrexed

cisplatin DRUG

75 mg/m2

cisplatin-pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed (non-squamous) NSCLC incurable locally advanced or metastatic (stage IIIB and stage IV) disease.
• Documented KRAS mutation
• 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.
• At least one unidimensionally measurable lesion meeting RECIST1.1.
• ECOG PS 0-2
• Age ≥ 18 years
• 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.
• Signed informed consent
• 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.

You may not qualify if:

• Pregnant or lactating women
• 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)
• History of hemoptysis ≥ grade 2 (bright red blood of at least 2,5 ml in the last 3 months)
• Evidence of tumor invading major blood vessels on imaging (i.e. superior vena cava or pulmonary artery)
• Patients with evidence or history of bleeding diathesis
• Non-healing wound or ulcer

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Dutch Society of Physicians for Pulmonology and Tuberculosis: collaborator

Study Sites (28)

VUmc Medical Center

Amsterdam, North Holland, 1081HV, Netherlands

Location

Medical spectrum Twente

Enschede, Overijssel, 7500 KA, Netherlands

Location

Meander Medical Center

Amersfoort, Utrecht, 3818 ES, Netherlands

Location

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Location

ZGT

Almelo, 7609 PP, Netherlands

Location

Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

OLVG

Amsterdam, 1090 HM, Netherlands

Location

Gelre Ziekenhuis

Apeldoorn, Netherlands

Location

Amphia Hospital

Breda, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Albert Schweitzer ziekenhuis

Dordrecht, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, 5631 BM, Netherlands

Location

Groene Hart

Gouda, Netherlands

Location

UMCG

Groningen, 9713 GZ, Netherlands

Location

Martini Ziekenhuis

Groningen, Netherlands

Location

Tergooi ziekenhuizen

Hilversum, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, 2130 AT, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Maasstad ziekenhuis

Rotterdam, 3007 AC, Netherlands

Location

St. Fransicus Gasthuis

Rotterdam, 3045 PM, Netherlands

Location

Haga

The Hague, 2545 CH, Netherlands

Location

Medical Center Haaglanden

The Hague, Netherlands

Location

Diakonessenhuis Utrecht

Utrecht, 3582 KE, Netherlands

Location

St. Antonius ziekenhuis

Utrecht, Netherlands

Location

VieCuri Medisch Centrum voor Noord-Limburg

Venlo, Netherlands

Location

Isala Klinieken

Zwolle, 8000 GK, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Paclitaxel; Bevacizumab; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Anne-Marie C Dingemans, MD PhD

  Dutch Society of Physicians for Pulmonology and Tuberculosis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: April 19, 2016
• Study Start: April 1, 2016
• Primary Completion: September 19, 2021
• Study Completion: April 1, 2024
• Last Updated: December 21, 2021

Record last verified: 2021-12

Locations

NL (28)