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

Carcinoma, Non-Small Cell Lung Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02743923
• Other study ID #: NVALT 22
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 2016
• Est. completion date: April 2024

Study information

• Verified date: December 2021
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 203
• Est. completion date: April 2024
• Est. primary completion date: September 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small Cell Lung
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• carboplatin
AUC 6
• paclitaxel
200mg/m2
• Bevacizumab
15 mg/kg
• Pemetrexed
500 mg/m2
• cisplatin
75 mg/m2

Locations

Country	Name	City	State
Netherlands	ZGT	Almelo
Netherlands	Meander Medical Center	Amersfoort	Utrecht
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	VUmc Medical Center	Amsterdam	Noord-Holland
Netherlands	Gelre Ziekenhuis	Apeldoorn
Netherlands	Amphia Hospital	Breda
Netherlands	Jeroen Bosch Hospital	Den Bosch
Netherlands	Haga	Den Haag
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Albert Schweitzer ziekenhuis	Dordrecht
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	Medical spectrum Twente	Enschede	Overijssel
Netherlands	Groene Hart	Gouda
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	UMCG	Groningen
Netherlands	Tergooi ziekenhuizen	Hilversum
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Maasstad ziekenhuis	Rotterdam
Netherlands	St. Fransicus Gasthuis	Rotterdam
Netherlands	Medical Center Haaglanden	the Hague
Netherlands	Diakonessenhuis Utrecht	Utrecht
Netherlands	St. Antonius ziekenhuis	Utrecht
Netherlands	VieCuri Medisch Centrum voor Noord-Limburg	Venlo
Netherlands	Isala Klinieken	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Dutch Society of Physicians for Pulmonology and Tuberculosis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	overall survival	Stratification for KRAS mutation (G12V versus G12C versus other)	date of randomization to the date of death from any cause, assessed up to 60 months.
Secondary	outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).	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.	date of randomization to the date of death from any cause, assessed up to 60 months.
Secondary	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

External Links

•   ESMO oral presentation sept 2021