Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02743923
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : November 14, 2018
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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 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
Study Start Date : April 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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


Contacts
Layout table for location contacts
Contact: Anne-Marie C Dingemans, MD PhD +31 433875047 a.dingemans@mumc.nl
Contact: A J de Langen, MD PhD +31 205122958 j.d.langen@nki.nl

Locations
Layout table for location information
Netherlands
VUmc Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1081HV
Contact: Idris Bahce, MD       i.bahce@vumc.nl   
Principal Investigator: Idris Bahce, MD         
Medical spectrum Twente Recruiting
Enschede, Overijssel, Netherlands, 7500 KA
Contact: Hugo Schouwink, MD       J.Schouwink@mst.nl   
Principal Investigator: Hugo Schouwink, MD         
Meander Medical Center Recruiting
Amersfoort, Utrecht, Netherlands, 3818 ES
Contact: Joop van den Brand, MD       JJG.vanden.Brand@meandermc.nl   
Principal Investigator: Joop van den Brand, MD         
ZGT Recruiting
Almelo, Netherlands, 7609 PP
Contact: Jeske Staal, MD       j.staal@zgt.nl   
Principal Investigator: Jeske Staal, MD         
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Egbert Smit       e.smit@nki.nl   
Principal Investigator: Egbert Smit, MD         
OLVG Not yet recruiting
Amsterdam, Netherlands, 1090 HM
Contact: A Moons, MD       A.Moons-Pasic@olvg.nl   
Principal Investigator: A Moons, MD         
Gelre Ziekenhuis Recruiting
Apeldoorn, Netherlands
Contact: Niels Pronk, MD       n.pronk@gelre.nl   
Principal Investigator: Niels Pronk, MD         
Amphia Hospital Recruiting
Breda, Netherlands
Contact: Nicolaas van Walree, MD       nwalree@amphia.nl   
Principal Investigator: Nicolaas van Walree, MD         
Jeroen Bosch Hospital Recruiting
Den Bosch, Netherlands
Contact: Bonne Biesma, MD       b.biesma@jbz.nl   
Principal Investigator: Bonne Biesma, MD         
Haga Recruiting
Den Haag, Netherlands, 2545 CH
Contact: Pepijn Brocken, MD       p.brocken@hagaziekenhuis.nl   
Principal Investigator: Pepijn Brocken, MD         
Deventer Ziekenhuis Recruiting
Deventer, Netherlands
Contact: Suzy Samii, MD       s.samii@dz.nl   
Principal Investigator: Suzy Samii, MD         
Albert Schweitzer ziekenhuis Recruiting
Dordrecht, Netherlands
Contact: Eric van Thiel, MD       EricvanThiel@asz.nl   
Principal Investigator: Eric van Thiel, MD         
Ziekenhuis Gelderse Vallei Recruiting
Ede, Netherlands
Contact: Wouter de Jong, MD       jongw@zgv.nl   
Principal Investigator: Wouter de Jong, MD         
Maxima Medisch Centrum Recruiting
Eindhoven, Netherlands, 5631 BM
Contact: Arjen van Henten, MD       a.vanhenten@mmc.nl   
Principal Investigator: Arjen van Henten, MD         
Groene Hart Recruiting
Gouda, Netherlands
Contact: ten Heuvel, MD       alexandra.ten.heuvel@ghz.nl   
Principal Investigator: ten Heuvel, MD         
UMCG Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Harry Groen, MD       h.j.m.groen@umcg.nl   
Principal Investigator: Harry Groen, MD         
Martini Ziekenhuis Recruiting
Groningen, Netherlands
Contact: John van Putten, MD       jwg.van.putten@mzh.nl   
Principal Investigator: John van Putten, MD         
Tergooi ziekenhuizen Recruiting
Hilversum, Netherlands
Contact: Jan Maarten van Haarst, MD       jvanhaarst@tergooi.nl   
Principal Investigator: Jan Maarten van Haarst, MD         
Spaarne Gasthuis Recruiting
Hoofddorp, Netherlands, 2130 AT
Contact: Frans Krouwels, MD       fkrouwels@spaarnegasthuis.nl   
Principal Investigator: Frans Krouwels, MD         
Medisch Centrum Leeuwarden Recruiting
Leeuwarden, Netherlands
Contact: Venmans, MD         
Principal Investigator: Venmans, MD         
Maastricht University Medical Center Recruiting
Maastricht, Netherlands
Contact: Anne-Marie Dingemans, MD       a.dingemans@mumc.nl   
Principal Investigator: Anne-Marie Dingemans, MD         
Maasstad ziekenhuis Recruiting
Rotterdam, Netherlands, 3007 AC
Contact: Susan van 't Westeinde, MD       westeindes@maasstadziekenhuis.nl   
Contact: , MD         
Principal Investigator: Susan van 't Westeinde, MD         
St. Fransicus Gasthuis Recruiting
Rotterdam, Netherlands, 3045 PM
Contact: Wessel Hanselaar, MD       w.hanselaar@franciscus.nl   
Principal Investigator: Wessel Hanselaar, MD         
Medical Center Haaglanden Recruiting
the Hague, Netherlands
Contact: Klaar Maas, MD       k.maas@mchaaglanden.nl   
Principal Investigator: Klaar Maas, MD         
Diakonessenhuis Utrecht Recruiting
Utrecht, Netherlands, 3582 KE
Contact: Leontine van Elden, MD       lvelden@diakhuis.nl   
Principal Investigator: Leontine van Elden, MD         
St. Antonius ziekenhuis Recruiting
Utrecht, Netherlands
Contact: Franz Schramel, MD       f.schramel@antoniusziekenhuis.nl   
Principal Investigator: Franz Schramel, MD         
VieCuri Medisch Centrum voor Noord-Limburg Recruiting
Venlo, Netherlands
Contact: Vivian van Kampen, MD       vvankampen@viecuri.nl   
Principal Investigator: Vivian van Kampen, MD         
Isala Klinieken Recruiting
Zwolle, Netherlands, 8000 GK
Contact: Jos Stigt       j.a.stigt@isala.nl   
Principal Investigator: Jos Stigt, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Dutch Society of Physicians for Pulmonology and Tuberculosis
Investigators
Layout table for investigator information
Principal Investigator: Anne-Marie C Dingemans, MD PhD Dutch Society of Physicians for Pulmonology and Tuberculosis

Layout table for additonal information
Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02743923     History of Changes
Other Study ID Numbers: NVALT 22
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
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
Albumin-Bound Paclitaxel
Cisplatin
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