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Chemotherapy in non-small cell lung cancer patients with a KRAS mutation in the tumor. Comparing two schedules: cisplatin-pemetrexed with carboplatin-paclitaxel-bevacizumab: NVALT 22

Phase 1
Conditions
Advanced non-small cell lung cancer
MedDRA version: 21.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2015-003121-34-NL
Lead Sponsor
Stichting NVALT studies
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
240
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. 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:
a.Adequate bone marrow reserve: ANC >= 1.5 x 109/L, platelets >= 100 x 109/L.
b.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
c.Renal: calculated creatinine clearance >= 60 ml/min based on the Cockroft-Gault formula.
d.Urine protein (dip-stick) < 2 +; when >=2 +: 24 hours urine protein <=1 gr.
8.Signed informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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
7.Surgical intervention within 28 days
8.History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
9.Patients who are poor medical risks because of non-malignant disease as well as those with active uncontrolled infection
10.Documented symptomatic brain metastases unless the patient has completed local therapy for central nervous system metastases.
11.Concomitant treatment with any other experimental drug under investigation.
12.Inability or unwillingness to take folic acid, vitamin B-12 supplementation or dexamethasone.
13.Previous or active concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study
14.History of HIV infection or chronic hepatitis B or C
15.Active clinically serious infection

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To compare two (standard) treatment regimens in patients with KRAS mutated, advanced stage NSCLC as first line treatment.;Secondary Objective: To investigate differences in overall response rate (ORR) and disease control rate. <br>To investigate differences in overall survival<br>To investigate differences in outcome between different subtypes of KRAS mutations<br>To investigate response by Crabb criteria<br>;Primary end point(s): Progression-free survival defined by the response criteria in solid tumors (RECIST) on CT scan.;Timepoint(s) of evaluation of this end point: Every 6 weeks
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Overall response rate <br>Overall survival;Timepoint(s) of evaluation of this end point: Every 6 weeks<br>Continuously
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