Evaluation of the efficacy of high throughput genome analysis as a therapeutic decision tool for patients with metastatic non small cell lung cancer - SAFIR 02 Lung

• Register: EUCTR
• Last refreshed on: 21 September 2015
• Main ID: EUCTR2013-001653-27-FR
• Date of registration: 16/09/2015
• Prospective Registration: No
• Primary sponsor: UNICANCER
• Public title: Evaluation of the efficacy of high throughput genome analysis as a therapeutic decision tool for patients with metastatic non small cell lung cancer - SAFIR 02 Lung
• Scientific title: Evaluation of the efficacy of high throughput genome analysis as a therapeutic decision tool for patients with metastatic non small cell lung cancer - SAFIR 02 Lung
• Date of first enrolment: 24/07/2014
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001653-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard maintenance treatments Number of treatment arms in the trial: 2

Countries of recruitment

France

Contacts

• Name: Marta JIMENEZ
• Affiliation: UNICANCER

• Name: Marta JIMENEZ
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients who received 4 cycles of an induction platinum-based chemotherapy and who are presenting a stable or a responding disease at the time of randomization
2. Patients who still meet the screening phase inclusion (except criteria 4) and exclusion criteria (except criteria 2)
3. Patients whose tumor sample is presenting at least one genomic alteration from the list of predefined targetable genomic alterations and for whom the multidisciplinary tumor board has provided a personalized guidance
4. Age > 25 years for patients planned to receive AZD4547
5. Patients will have had at least a 28-day washout period from the platinum-based regimen prior to randomization and should have recover (grade =1) from all residual toxicities, excluding alopecia.
6. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, beginning 2 weeks before the first dose of investigational product and for at least 3 months after the last dose of study drug.
7. Women of childbearing potential must have a negative serum pregnancy test done within 14 days and/or urine pregnancy test 72 hours prior to the administration of the study drug
8. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 3 months after the last dose.
9. Provision of signed and dated, written informed consent prior to randomization and to any study specific procedures, sampling and analyses
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 115
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 115

Exclusion criteria:
1. No “targetable” genomic alteration identified during the screening phase (either due to the lack of alteration or due to ineligible samples for genomic analysis) or unfavorable decision from the multidisciplinary tumor board to drive the patient to the randomization
2. Life expectancy < 3 months.
3. Disease progression or toxicity that led to the discontinuation of the platinum-based chemotherapy before 4 full cycles have been delivered, or disease progression occurring between the end of chemotherapy and randomization
4. Major surgery within 30 days (excluding placement of vascular access) or minor surgery within 14 days prior to randomisation
5. Less than 28 days from radiotherapy (wide field of radiation), less than 2 weeks from palliative radiation (limited fields). Fields should not have involved all target lesions
6. Patients previously treated in the last 30 days with a targeted agent in the same class as agents tested in this study
7. Participation to another clinical study with an investigational product (IP) during the last 30 days
8. History of hypersensitivity to active or inactive excipients of one of the study drugs
9. Toxicities of grade =2 from any previous anti-cancer therapy, with the exception of alopecia
10. Altered haematopoietic or organ function, as indicated by the following criteria:
- Polynuclear neutrophils < 1.5 x 109/L
- Platelets < 100 x 109/L
- Haemoglobin < 90 g/L
- ALAT/ASAT > 2.5x ULN in the absence of or > 5x ULN in the presence of liver metastases
- bilirubin > 1.5xULN
- creatinine clearance =50 mL/min (measured or calculated by Cockroft and Gault formula)
- Proteinuria > 3+ on dipstick analysis or > 3.5g/24 hours or a urine protein/creatinine ratio > 3.5 (only for patients dried to receive AZD5363)
- Sodium, magnesium, calcium and phosphate > ULN
- Potassium < 4 mmol/L
- glycosylated haemoglobin (HbA1C) = 8.0% (64 mmol/mol), (only for patients dried to receive AZD5363)
- Fasting Plasma Glucose = 7.0 mmol/L(126 mg/dL) (fasting is defined as no calorie intake for at least 8 hours)
11. Any of the following additional cardiac criteria:
- Mean resting corrected QT interval (QTc)>480msec (or QTcF >450 msec) obtained from 3 consecutive ECGs
- LVEF <50% (MUGA scan or Echocardiogram),
12. Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with :
- AZD4547 : current evidence or previous history of retinal pigmented epithelium detachment (RPED), previous laser treatment or intra-ocular injection for treatment of macular degeneration, current evidence or previous history of dry or wet age-related macular degeneration, current evidence or previous history of retinal vein occlusion (RVO), current evidence or previous history of retinal degenerative diseases (eg, hereditary), current evidence or previous history of any other clinically relevant chorioretinal defect
- AZD8931 : any eye injury in the previous 3 months or a prior eye injury still associated with persistent or recurrent symptoms or impairment of vision, corneal surgery (laser refractive surgery performed more than 3 months prior to the start of the trial is allowed and should be recorded in surgical history), orbital irradiation, collagen vascular, chronic inflammatory or degenerative disease with eye involvement (eg, rheumatoid, Sjögren’s syndrome, systemic lupus erythematosus [SLE]), clinically significant ocular surface disease i.e. diseases of the conjunctiva an

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Patients with metastatic non small cell lung cancer (NSCLC) in 1st line chemotherapy
MedDRA version: 18.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: AZD2014
Pharmaceutical Form: Tablet

Product Name: AZD4547
Pharmaceutical Form: Tablet

Product Name: AZD5363
Pharmaceutical Form: Capsule

Product Name: AZD8931
Pharmaceutical Form: Tablet

Product Name: Selumetinib
Pharmaceutical Form: Capsule

Trade Name: CAPRELSA
Product Name: Vandetanib
Product Code: ZD6474
Pharmaceutical Form: Tablet
CAS Number: 443913-73-3
Current Sponsor code: VANDETANIB
Other descriptive name: VANDETANIB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 50-300

Primary Outcome(s)

Secondary Objective: - To compare overall survival,
- To compare overall response rates and changes in tumor size,
- To evaluate safety,
- To explore the efficacy (response rate, change in tumor size, progression-free survival, overall survival) of each individual targeted agent,
- To correlate molecular mechanisms in patients with the efficacy endpoints (response rate, progression-free and overall survival)

Main Objective: To evaluate whether treatment with targeted agents guided by high throughput molecular analyses (CGH array, next generation sequencing) improves overall progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC.

Primary end point(s): Anti-tumor activity of all the agents, as the primary objective of the trial, will be carried out by the determination of the progression-free survival assessed in each arm of treatment.
Progression-free survival (PFS) is defined as the time from randomization to the first documented progression of disease or death, whatever the cause. The tumor assessments are made by the investigators based on RECIST 1.1 criteria ([Eisenhauer 2009]). Patients still alive at the time of analysis without documented progression (including lost of follow-up) will be censored at the last known alive date.

Secondary Outcome(s)

Secondary end point(s): Overall Survival :
Overall Survival (OS) is defined as the time from randomization to death due to any cause. Patients still alive at the time of analysis (including lost of follow-up) will be censored at the last known alive date.

Response and change in tumor size:
Objective response (i.e. complete or partial response) will be defined using RECIST V1.1 criteria.
Changes in tumor size over time will also be analysed.

Safety :
Evaluation of safety will be done according to NCI CTCAE v4.03 criteria.

Secondary ID(s)

UC_0105-1305_/_IFCT_1301

Source(s) of Monetary Support

Astra Zeneca Laboratories