Study with investigational drug PF-06463922 and comparator crizotinib in patients with a specific type of advanced lung cancer

Phase 1

• Conditions: Advanced ALK positive non small cell lung cancer; MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 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); MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003315-35-GB
• Lead Sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-15
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 280

Inclusion Criteria

1.Diagnosis:
a.Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC where ALK status is determined by the FDA-approved (for use in US) and CE (Conformité Européene)marked (for use ex-US) Ventana ALK (D5F3) CDx Assay;
b.Tumor Requirements: At least 1 extracranial measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. CNS metastases are allowed if:
i.Asymptomatic: either not currently requiring corticosteroid treatment, or on a stable or decreasing dose of = 10 mg QD prednisone or equivalent; or
ii.Previously diagnosed and treatment has been completed with full recovery from the acute effects of radiation therapy or surgery prior to randomization, and if corticosteroid treatment for these metastases has been withdrawn for at least 4 weeks with neurological stability; or
iii.Leptomeningeal disease (LMD) or carcinomatous meningitis (CM) if visualized on MRI (magnetic resonance imaging), or if baseline CSF positive cytology is available.
c.Tissue Requirements: All patients must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected prior to randomization. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed.
2.No prior systemic NSCLC treatment, including molecularly targeted agents, angiogenesis inhibitors, immunotherapy, or chemotherapy. Adjuvant/neoadjuvant NSCLC treatment only allowed if completed more than 12 months prior to randomization.
3.Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2.
4.Age =18 years (or =20 years as required by local regulation).
5.Adequate Bone Marrow Function, including:
a.Absolute Neutrophil Count (ANC) = 1,500/mm3 or = 1.5 x 109/L;
b.Platelets =100,000/mm3 or =100 x 109/L;
c.Hemoglobin = 9 g/dL.
6.Adequate Pancreatic Function, including:
a.Serum total amylase = 1.5 x upper limit of normal (ULN)*;
b.Serum lipase = 1.5 x ULN.
*if total amylase > 1.5 x ULN, but pancreatic amylase is within the ULN, then patient may be enrolled
7.Adequate Renal Function, including:
a.Serum creatinine = 1.5 x ULN or estimated creatinine clearance = 60 mL/min as calculated using the method standard for the institution.
8.Adequate Liver Function, including:
a.Total serum bilirubin = 1.5 x ULN;
b.Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 2.5 x ULN (= 5.0 x ULN in case of liver metastases);
9.Acute effects of prior radiotherapy resolved to baseline severity or to CTCAE Grade =1 except for AEs that in the investigator’s judgment do not constitute a safety risk for the patient.
10.Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria:
•Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormo

Exclusion Criteria

1.Spinal cord compression unless the patient has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks prior to randomization.
2.Major surgery within 4 weeks prior to randomization. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
3.Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Patients who complete whole brain irradiation within 4 weeks prior to randomization or palliative radiation therapy outside of the CNS within 48 hours prior to randomization will also not be included in the study.
4.Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes.
5.Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations.
6.Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (e.g., in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
7.Clinically significant cardiovascular disease, that is, active or within 3 months prior to enrollment: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class = II), second- degree or third-degree AV block (unless paced) or any AV block with PR >220 msec; or
Ongoing cardiac dysrhythmias of NCI CTCAE Grade = 2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
8.Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease) in the last month prior to randomization.
9.History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis.
10.Evidence of active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, lobular carcinoma in situ/ductal carcinoma in situ (LCIS/DCIS) of the breast, or localized prostate cancer) within the last 3 years prior to randomization.
11.Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days prior to the first dose of lorlatinib or crizotinib.
a.known strong CYP3A inhibitors (eg, atazanavir, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavi

Study & Design

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