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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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13 December 2021 |
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Main ID: |
EUCTR2007-006682-33-FR |
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Date of registration:
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25/03/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Randomzied Phase 2 Trial of AG-013736 or Bevacizumab in Combination with Paclitaxel and Carboplatin as First Line Treatment For Patients with Advanced Non-small Cell Lung Cancer
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Scientific title:
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Randomzied Phase 2 Trial of AG-013736 or Bevacizumab in Combination with Paclitaxel and Carboplatin as First Line Treatment For Patients with Advanced Non-small Cell Lung Cancer |
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Date of first enrolment:
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29/05/2008 |
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Target sample size:
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108 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006682-33 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Czech Republic
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France
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Spain
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
1. Histologically or cytologically confirmed diagnosis of advanced non-squamous cell, NSCLC with documented Stage IIIB with pleural effusion, or Stage IV or recurrent disease
2. At least one site of measurable disease (per RECIST). Measurable disease that has been previously irradiated will not be considered a target lesion unless the lesion diameter has grown by =20 % since completion of the prior radiation therapy or if the lesion is a new lesion, assuming all other criteria are met
3. No prior systemic treatment for NSCLC except prior adjuvant therapy if last dose was >12 months prior to enrollment
4. Adequate organ function as determined by the following criteria:
- Absolute neutrophil count (ANC) =1500 cells/mm3
- Platelet count =100,000 cells/mm3
- Hemoglobin =9 g/dL
- Serum creatinine =1.5 x upper limit of normal (ULN) or calculated creatinine clearance = 60 mL/min
- AST and ALT <2.5 x ULN, or AST and ALT <5 x ULN if liver function abnormalities are due to underlying malignancy
- Total bilirubin =1.5 x ULN
- Urine protein:creatinine ratio <0.5
5. Age =18 years
6. ECOG performance status of 0 or 1
7. Life expectancy =12 weeks
8. Prior surgery or radiation therapy is permitted. Radiation therapy must have completed =21 days or major surgery =28 days prior to start of treatment. All acute toxicities must have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0). Fine needle aspiration procedures (if necessary) must have been completed =7 days prior to treatment.
9. Female patients may not be pregnant or breastfeeding. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of patient reported outcome measures.
11. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment.
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. Histologic evidence of predominantly squamous-cell NSCLC
2. Prior treatment with systemic therapy for advanced disease
3. Prior treatment with a VEGF or VEGFR inhibitor
4. Preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
5. Known central nervous system (CNS) metastasis
- CNS imaging is not required at baseline for patients who have no symptoms suggestive of CNS metastases.
6. Current or recent (within 1 month) use of a thrombolytic agent.
7. History of a hematologic diathesis or coagulopathy within 6 months of study entry
8. Need for therapeutic anticoagulation (at time of screening)
9. Regular use of aspirin (>325 mg/day) or NSAID use or use of other medications known to inhibit platelets
10. History of hemoptysis > ½ tsp of bright red blood per day within 1 week of enrollment
11. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism.
12. Gastrointestinal abnormalities including:
- inability to take oral medication
- requirement for intravenous alimentation
- prior surgical procedures affecting absorption including gastric resection
- treatment for active peptic ulcer disease in the past 6 months
- active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
- malabsorption syndromes
13. Active malignancies other than NSCLC
14. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, itraconazole, erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) is not permitted
15. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John’s wort) is not permitted. (Note: The short term use of dexamethasone as a premedication for chemotherapy is not an exclusion criterion)
16. Acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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First line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC)
MedDRA version: 9.1
Level: PT
Classification code 10059515
Term: Non-small cell lung cancer metastatic
MedDRA version: 9.1
Level: LLT
Classification code 10029515
Term: Non-small cell lung cancer recurrent
MedDRA version: 9.1
Level: LLT
Classification code 10029521
Term: Non-small cell lung cancer stage IIIB
MedDRA version: 9.1
Level: PT
Classification code 10029522
Term: Non-small cell lung cancer stage IV
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Intervention(s)
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Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Axitinib
CAS Number: 319460-85-0
Current Sponsor code: AG-013736
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Axitinib
CAS Number: 319460-85-0
Current Sponsor code: AG-013736
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Trade Name: Avastin
Product Name: bevacizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
CAS Number: 216974-75-3
Other descriptive name: Recombinant humanised monoclonal antibody to VEGF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Trade Name: Paxene
Product Name: paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-
Trade Name: Carboplatine Mayne
Product Name: carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
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Primary Outcome(s)
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Secondary Objective: - Assess the Overall Survival (OS) in each arm;
- To assess the overall response rate (ORR) in each arm;
- Estimate the duration of response (DR) in each arm;
- Evaluate the safety and tolerability of AG-013736 in combination with paclitaxel and carboplatin;
- Conduct population PK analysis using AG-013736 plasma concentrations;
- Evaluate the HRQoL and lung cancer/treatment related symptoms of patients in each arm according to European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and Quality of Life Questionnaire Lung Cancer 13 (QLQ LC 13).
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Primary end point(s): Primary Endpoint:
- Progression Free Survival (PFS) defined as the time from randomization to the date of progression or death due to any cause, whichever occurs first.
Secondary Endpoints:
- Overall Survival (OS) defined as the time from randomization to the date of death due to any cause.
- Overall confirmed objective response rate (ORR) defined as the proportion of randomized patients with a confirmed best response characterized as either a complete response (CR) or partial response (PR) (target lesions and tumor response defined according to RECIST guidelines). Confirmed responses are those that persist on a follow up imaging assessment =4 weeks after the initial objective documentation of response.
- Duration of response (DR) defined as the time from first documentation of response to the date of progression or death due to any cause, whichever occurs first.
- Overall safety profile characterized by type, frequency, severity (as graded using NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE), v3.0 and relationship to study therapy of adverse events and laboratory abnormalities.
- Population pharmacokinetic analysis using AG-013736 plasma concentrations.
- Patient Reported Outcome (PRO) changes in scores for HRQoL and lung cancer/treatment related symptoms according to European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and Quality of Life Questionnaire Lung Cancer 13 (QLQ LC 13)
- Molecular Profiling and Biomarkers of AG-013736 mechanism of action and clinical benefit will be explored with optional pharmacogenomic and gene expression profiling in whole blood. VEGF receptor and associated signaling pathways will be explored using circulating endothelial cells and soluble proteins in blood.
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Main Objective: To assess progression free survival (PFS) of AG-013736 in combination with paclitaxel and carboplatin (Arm A) versus bevacizumab in combination with paclitaxel and carboplatin (Arm B).
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Secondary ID(s)
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2007-006682-33-GB
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A4061030
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 29/05/2008
Contact:
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