A Phase 3, randomized, open label study of lorlatinib (PF 06463922) monotherapy versus crizotinib monotherapy in the first line treatment of patients with advanced ALK positive non small cell lung cancer
- Conditions
- advanced ALK positive non small cell lung cancerNon small cell lung cancer1003866610029107
- Registration Number
- NL-OMON54681
- Lead Sponsor
- Pfizer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 8
see section 4.1 in protocol:
1.Diagnosis:
a.Study Population: Patients with histologically or cytologically confirmed
diagnosis of locally advanced [(Stage IIIB not amenable for multimodality
treatment) or metastatic (Stage IV) by American Joint Committee on Cancer
(AJCC) v 7.0] ALK-positive NSCLC where ALK status is determined by the
FDA-approved (for use in US), CE (Conformité Européene) marked (for EU and
other countries that accept CE marking), and PMDA(Pharmaceuticals and Medical
Devices Agency)- approved (for use in Japan) Ventana ALK (D5F3) Companion
Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT platforms (refer
to Section 6.1.1.1 for any prescreening activity related to ALK determination);
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and if corticosteroid treatment for these metastases has been withdrawn for at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 participants 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 participant.
10. Serum pregnancy test (for females of childbearing potential) negative at
screening. Female participants of non-childbearing potential must meet at least
1 of the foll
See protocol section 4.2:
Patients with any of the following characteristics/conditions will not be
included in the study:
1. Spinal cord compression unless the participant 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 vascular (both arterial and venous) and nonvascular
cardiac conditions, (active or within 3 months prior to enrollment), which may
include, but are not limited to:
- Arterial disease such as cerebral vascular accident/stroke (including
Transient Ischemic Attack -TIA), myocardial infarction, unstable angina;
- Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary
embolism;
-Non-vascular cardiac disease such as 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 participant is otherwise healthy
such as long-distance runners, etc.), machine-read Electrocardiogram (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 pros
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS based on blinded independent central review (BICR) assessment (RECIST<br /><br>v.1.1).</p><br>
- Secondary Outcome Measures
Name Time Method