An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

• Register: EUCTR
• Last refreshed on: 16 February 2015
• Main ID: EUCTR2009-012595-27-SE
• Date of registration: 03/09/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene
• Scientific title: PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF THE EFFICACY AND SAFETY OF PF 02341066 VERSUS STANDARD OF CARE CHEMOTHERAPY (PEMETREXED OR DOCETAXEL) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING A TRANSLOCATION OR INVERSION EVENT INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK) GENE LOCUS
• Date of first enrolment: 14/10/2010
• Target sample size: 318
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012595-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, China, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov call center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov call center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or
metastatic
2. Positive for translocation or inversion events involving the ALK gene locus (e.g.
resulting in EML4-ALK fusion) as determined by an ALK break apart FISH assay and
defined by an increase in the distance of 5’ and 3’ ALK probes or the loss of the 5’ probe
3. Patients must have had progressive disease after only one prior chemotherapy regimen. This regimen must have been platinum-based and may have included maintenance therapy. Patients must be considered appropriate candidates for additional chemotherapy with either single-agent pemetrexed or single-agent docetaxel Includes patients who received one prior platinum-based chemotherapy for treatment of de novo Stage IIIB/IV NSCLC.
- Includes patients who have received one prior platinum-based chemotherapy in the adjuvant setting following surgical resection for early disease and whose disease has recurred within 6 months of completion of prior chemotherapy
- Includes patients who received one prior platinum-based chemotherapy in
combination with radiation therapy for Stage III locoregional disease and whose
disease has recurred within 6 months of completion of prior chemotherapy
- Includes patients who received 2 prior platinum-based chemotherapy regimens, if the first regimen was given as adjuvant therapy or was given in combination with
radiation therapy for locally advanced disease
- Includes patients who have received prior treatment with an EGFR tyrosine kinase
inhibitor, such as erlotinib or gefitinib, providing these patients have also received
only one prior platinum-based chemotherapy regimen as in one of the scenarios
described above
4. Patients with brain metastases are eligible if asymptomatic or if treated must be neurologically stable for at least 2 weeks and is not taking any medications contraindicated in Exclusion Criteria #12, 13, 14.
5. Any prior chemotherapy or major surgeries must have been completed at least 4 weeks prior to initiation of study medication. Any prior radiation (except for palliative)or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of study medication. Palliative radiation (= 10 fractions) must have been
completed 48 hours prior to the start of study treatment. Any acute toxicity must have recovered to = Grade 1 (except alopecia)
6. Tumors must have measurable disease as per RECIST (version 1.1);
7. Female or male, 18 years of age or older (for patients enrolled in Japan: consent from a legally acceptable representative is required for all patients who are under 20 years old)
8. ECOG performance status 0-2
9. Adequate organ function as defined by the following criteria: Hepatic function
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =2.5 x
upper limit of normal (ULN), or AST and ALT =5 x ULN if liver function
abnormalities are due to underlying malignancy; however, for patients who if
randomly assigned to Arm B must receive docetaxel, ALT and/or AST must not be >
1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN
-Total serum bilirubin =1.5 x ULN however for patients who if randomly assigned to
Arm B must receive docetaxel, total serum bilirubin must be = 1 x ULN
Bone marrow function
- Absolute neutrophil count (ANC) =1500/µL
- Platelets =100,000/µL
- Hemoglobin =8.0 g/dL
Renal function
- Creatinine clearance (based on modified Cockcrof
Exclusion criteria:
1. Current treatment on another therapeutic clinical trial
2. Prior therapy specifically directed against ALK
3. Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease
4. Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
5. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec
6. Previous treatment with PF-02341066
7. Patients who if randomly assigned to Arm B must receive pemetrexed and who have NSCLC with predominantly squamous cell carcinoma
8. Patients who if randomly assigned to Arm B must receive docetaxel and who have
peripheral neuropathy with Grade > 2
9. Patients who if randomly assigned to Arm B must receive docetaxel and who have had a hypersensitivity reaction to medications formulated with polysorbate 80
10. [Deleted per Amendment #7]
11. Pregnancy or breastfeeding.
12. Use of drugs or foods that are known potent CYP3A4 inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole,ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole and grapefruit or
grapefruit juice

13. Use of drugs that are known potent CYP3A4 inducers, including but not limited to
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s wort

14. Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited di hydroergotamine, ergotamine, pimozide, astemizole*, cisapride*, and terfenadine* (* withdrawn from U.S. market)

15. Prior malignancy (other than current NSCLC): patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or localized cervical cancer, or localized and presumed cured prostate cancer) within the last 3 years
16. For Japan only: patients who have following complications or symptoms:
- Serious wound such as chronic wound, or grade =3 gastrointestinal ulcer
- Serious gastrointestinal symptoms such as grade =3 diarrhea
17. Other severe acute or chronic medical or psychiatric conditions, or laboratory
abnormalities that would impart, in the judgment of the investigator and/or sponsor,
excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.


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

Health Condition(s) or Problem(s) studied

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

ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING A TRANSLOCATION OR INVERSION EVENT INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK) GENE LOCUS
MedDRA version: 15.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Not Applicable
Product Code: crizotinib
Pharmaceutical Form: Tablet
INN or Proposed INN: crizotinib
CAS Number: 877399-52-5.
Current Sponsor code: PF-02341066
Other descriptive name: IUPAC: (R)-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Not Applicable
Product Code: crizotinib
Pharmaceutical Form: Tablet
INN or Proposed INN: crizotinib
CAS Number: 877399-52-5.
Current Sponsor code: PF-02341066
Other descriptive name: IUPAC: (R)-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Alimta (pemetrexed)
Product Name: Pemetrexed
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: pemetrexed
CAS Number: 137281-23-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Taxotere (docetaxel)
Product Name: Docetaxel
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: docetaxel
CAS Number: 114977-28-5
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 80-

Trade Name: Taxotere (docetaxel)
Product Name: Docetaxel
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: docetaxel
CAS Number: 114977-28-5
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: Secondary Objectives:
•To compare secondary measures of clinical efficacy including overall survival (OS),
objective response rate (ORR), and disease control rate (DCR) between the two treatment groups, and evaluate duration of response (DR) and time to tumor response (TTR)
•To assess the safety and tolerability of PF-02341066 compared to pemetrexed or docetaxel
•To compare PRO of HRQoL, disease/treatment-related symptoms of lung cancer, and general health status in both treatment arms
•To characterize the effects of PF-02341066 at therapeutic doses on QT interval in this patient population
•To determine PK in this patient population using POPPK methods and explore correlations between PK, response and/or safety findings
•To explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript
•To correlate modulation of soluble biomarkers to PK and outcome measures

Primary end point(s): Primary Endpoint:
? PFS based on RECIST version 1.1 (confirmed by independent radiology review)
Secondary Endpoints:
? 6-months and 1-year OS, OS, ORR (confirmed by independent radiology review), DCR at 6 and 12 weeks, DR
? Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities
? Plasma concentrations of PF-02341066
? QTc
? Types of EML4-ALK fusion variants and ALK protein expression
? Plasma concentrations of soluble c-Met ectodomain and HGF scatter proteins
? TTD in patient reported pain, dyspnea, and cough
? HRQoL, lung cancer disease/treatment-related symptoms, and general health status

Timepoint(s) of evaluation of this end point: randomization to date of first documentation of objective disease progression or date of death, whichever occurs first (for Progression Free Survival endpoint)

Main Objective: Primary Objective:
•To demonstrate that PF-02341066 (Arm A) is superior to standard of care chemotherapy, pemetrexed or docetaxel (Arm B), in prolonging PFS in patients with advanced NSCLC whose tumors harbor a translocation or inversion event involving the ALK gene locus and who have received only one prior chemotherapy regimen for advanced NSCLC and this regimen must have been platinum-based

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: randomization to date of death (for Overall Survival endpoint) date of first documentation of objective response that is subsequently confirmed to date of first documentation of objective disease progression or death, whichever occurs first (for Duration of Response endpoint)

Secondary end point(s): • 6-month and 1-year OS, OS, ORR (confirmed by independent radiology review), DCR at 6 and 12 weeks, DR and TTR.
• Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities.
• Plasma concentrations of PF-02341066.
• QTc.
• Types of EML4-ALK fusion variants and ALK protein expression.
• Plasma concentrations of soluble c-Met ectodomain and HGF scatter proteins.
• Time to deterioration (TTD) in patient reported pain, dyspnea, and cough.
• HRQoL, lung cancer disease/treatment-related symptoms, and general health status.

Secondary ID(s)

2009-012595-27-GB

A8081007

Source(s) of Monetary Support

Pfizer Inc