Ensayo fase II, doble ciego, aleatorizado, controlado con placebo, para evaluar la eficacia de AZD6244 (hidrógeno-sulfato), en combinación con Docetaxel, comparado con Docetaxel en monoterapia, en pacientes con cáncer de pulmón no microcítico localmente avanzado o metastásico (estadío IIIB - IV) con mutación KRAS positiva en 2ª línea de tratamientoA Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 (Hyd-Sulfate) in Combination with Docetaxel, Compared with Docetaxel Alone, in 2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV)

Phase 1

• Conditions: 2ª línea de tratamiento en pacientes con cáncer de pulmón no microcítico localmente avanzado o metastásico (estadío IIIB - IV) con mutación KRAS positiva 2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV); MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: LLTClassification code 10029522Term: Non-small cell lung cancer stage IV; MedDRA version: 9.1Level: LLTClassification code 10059515Term: Non-small cell lung cancer metastatic

• Registration Number: EUCTR2008-006323-31-ES
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-02-18
• Study Completion: 2011-09-22
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

1.Provision of signed, written and dated informed consent prior to any study specific procedures
2.Male or female, aged 18 years or older
3.Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
4.Failure of 1st line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) in advanced disease or subsequent relapse of disease following 1st line therapy. See Appendix L for further details. See Section 5.2 for specific 1st line agents not permitted in this study.
5.WHO Performance Status 0 ? 1
6.Patients must be eligible to receive treatment with docetaxel in accordance with docetaxel product information (available from Sanofi-Aventis, the manufacturer of docetaxel ? see Appendix J for contact details)
7.At least one lesion, not previously irradiated, that can be accurately measured as ?10 mm in the longest diameter (LD) with spiral computed tomography (CT) scan or as ?20 mm with conventional techniques (conventional CT, MRI) and which is suitable for accurate repeated measurements
8.Tumour sample confirmed as KRAS mutation positive (Note: Sample must be available upon enrolment to ship to AZ appointed central laboratory, or mutation status confirmed locally at AstraZeneca agreed local laboratory using a) allele specific PCR (this includes ARMS?) or b) direct sequencing)
9.Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Post menopausal females are defined as follows: natural menopause with menses >1 year ago; or radiation-induced oophorectomy with last menses >1 year ago; or chemotherapy-induced menopause with 1 year interval since last menses; or serum FSH and LH and plasma oestradiol levels in the postmenopausal range for the institution; or bilateral oopherectomy or hysterectomy.
10.Serum creatinine clearance >50mL/min by either Cockcroft-Gault formula or 24hr urine collection analysis
11.Patients should be able to swallow AZD6244/placebo capsules.
12. For inclusion in the optional host genetics research study patients must fulfil the following criteria: Provision of optional host genetics research informed consent. If a patient declines to participate in the host genetics research, there will be no penalty or loss of benefit to the patient. A patient who declines host genetics research participation will not be excluded from any other aspect of the main study.
13. For inclusion in the optional biomarkers research study patients must fulfil the following criteria: Provision of optional consent for use of residual KRAS tumour and CFDNA serum and plasma samples for additional biomarker research. If a patient declines to participate in the biomarkers research, there will be no penalty or loss of benefit to the patient. A patient who declines biomarkers research participation will not be excluded from any other aspect of the main study.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2.Previous randomisation of treatment in the present study
3.Mixed small cell and non-small cell lung cancer histology
4.Received >1 prior anti-cancer therapy for advanced or metastatic NSCLC (excluding radiotherapy, see exclusions 6 and 9)
5.Having received an investigational drug within the 30 days prior to entry, or have not recovered from side effects of an investigational drug
6.Receiving or have received systemic anti-cancer therapy within 4 weeks prior to starting study treatment (6 weeks for nitrosoureas, mitomycin, and suramin)
7.Prior treatment with a MEK inhibitor or any docetaxel containing regimen (prior treatment with paclitaxel is acceptable)
8.Any unresolved toxicity >CTCAE Grade 2 from previous anti-cancer therapy, apart from alopecia
9.The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 2 weeks of the first dose of study treatment
10.Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment
11.History of hypersensitivity to AZD6244, docetaxel, or any excipient of these agents
12.Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 3 months
13.Laboratory values as listed below (from laboratory results at Visit 1):
-ANC <1.5 x 109/L (1500 per mm3)
-Platelets <100 x 109/L (100,000 per mm3)
-Haemoglobin ?9.0 g/dL
-Serum bilirubin >Upper Limit of Normal (ULN)
-AST or ALT:
§>2.5 x ULN if no liver metastasis
§Between 3.5 x ULN and 5 x ULN, if liver metastasis present and ALP >6 x ULN
§>5 x ULN, if liver metastasis present
14.Cardiac conditions as follows:
-Uncontrolled hypertension (BP ?150/95 despite optimal therapy)
-Heart failure NYHA Class II or above
-Prior or current cardiomyopathy
-Baseline LVEF ?50%
-Atrial fibrillation with heart rate >100 bpm
-Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
15.Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
16.Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
17.History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
18.Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
19.Clinical judgement by the investigator that the patient should not participate in the study
Exclusion criteria for participation in the optional host genetics research component of the study:
1.Previous allogeneic bone marrow transplant
2.Whole blood transfusion within 120 days of the date of host genetic sample collection (except for leukocyte depleted blood transfusion, which is allowed).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified