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

Phase 1

• Conditions: metastatic non-small cell lung cancer; MedDRA version: 17.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-012504-13-DE
• Lead Sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017 US

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-02
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1100

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
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 (eg, 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. Once Amendment #10 is
approved at an individual site's IRB/EC, positive ALK results from other methods such as Immunohistochemistry (IHC) or Reverse Transcriptase Polymerase Chain Reaction (RT-PC) testing may also be acceptable after discussion and approval by the Sponsor.
3. Meets one of the following criteria:
Randomized to Arm B (pemetrexed or docetaxel) of Study A8081007 and
was discontinued from treatment due to RECIST version 1.1-defined
progression of disease as determined by independent radiology review.
Once the primary endpoint of Study A8081007 has been analyzed and
the results made available, patients randomized to Arm B of Study
A8081007 will be offered treatment with PF-02341066 and allowed to
enroll in Study A8081005 without RECIST version 1.1-defined
progression of disease as determined by independent radiology review.
However, upon IRB/EC approval of Amendment 14, patients will not be allowed to cross over from the chemotherapy arm of Study A8081007 without RECIST version 1.1 - defined progression of diease by independent radiology review.
Ineligibility for A8081007 due to (1) prior treatment for advanced
disease with more than one chemotherapy regimen, (2) prior treatment
with only one chemotherapy regimen for advanced disease and that
regimen was not platinum-based, (3) prior treatment with pemetrexed
as part of their platinum-based chemotherapy and did not meet the
docetaxel eligibility requirements from Protocol A8081007, (4) treated
with docetaxel as part of their platinum-based prior chemotherapy but
have NSCLC that is predominantly squamous cell carcinoma and thus,
not eligible to be dosed with pemetrexed, or (5) ECOG performance
status 3 or the laboratory or RECIST eligibility criteria (but must meet all
eligibility criteria of this protocol).
Once A8081007 enrollment is closed, patients with only one previous
treatment including single agent EGFR tyrosine kinase inhibitor, such as
erlotinib or gefitinib, for locally advanced or metastatic NSCLC can be
enrolled.
4. Patients with brain metastases are eligible if asymptomatic or if
treated must be neurologically stable for at least 2 weeks and are not
taking any medications contraindicated in Exclusion Criteria #11-13.
5. Any prior treatment (chemotherapy, radiation [except for palliative] or surgery)must have been completed at least 2 weeks prior to 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 been
recovered to = Grade 1 (except alopecia).
6. Tumors must have measurable disease as per RECIST (version 1.1);
see Appendix 6. Once Amendment #10 is approved by an individual's
IRB/EC, this criterion will no longer be required.
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 0-3.
9. Adequa

Exclusion Criteria

Patients presenting with any of the following will not be included in the trial:
1. Eligibility for Protocol A8081007 until enrollment is closed.
2. No prior systemic treatment, chemotherapy or EGFR tyrosine kinase
inhibitor for advanced NSCLC.
3. Current treatment on another therapeutic clinical trial.
4. Prior therapy specifically directed against ALK.
5. Spinal cord compression unless treated with the patient attaining
good pain control and stable or recovered neurologic function,
carcinomatous meningitis, or leptomeningeal disease.
6. 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.
7. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled
atrial fibrillation of any grade, or QTc interval >470 msec.
8. Previous treatment with PF-02341066.
9. [Deleted per Amendment #7].
10. Pregnancy or breastfeeding.
11. 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.
12. Use of drugs that are known potent CYP3A4 inducers, including but
not limited to carbamazepine, phenobarbital, phenytoin, rifabutin,,
rifampin, and St. John's wort.
13. Use of drugs that are CYP3A4 substrates with narrow therapeutic
indices, including but not limited to dihydroergotamine, ergotamine,
pimozide, astemizole*, cisapride*, and terfenadine* (* withdrawn from
U.S. market).
14. Prior malignancy (other than current NSCLC): patients will not be eligible if they have evidence of active malignancy (other than nonmelanoma skin cancer or localized cervical cancer, or localized and
presumed cured prostate cancer) within the last 3 years.
15. 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.
16. 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.
17. Patients with known interstitial fibrosis or interstitial lung disease.

Study & Design

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