Study of Lorlatinib In Participants with Anaplastic Lymphoma Kinase (ALK) -Positive NSCLC
- Conditions
- ALK-positive metastatic non-small-cell lung cancerMedDRA version: 21.1Level: 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
- EUCTR2019-002504-41-GB
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 70
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Participant must be =18 years of age inclusive (or = 20 years of age if required by local regulation), at the time of signing the informed consent.
2. Participants must have evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, American Joint Committee on Cancer [AJCC] v7.0) that carries an ALK rearrangement, as determined by FDA approved fluorescence in situ hybridization assay or by Immunohistochemistry.
3. disease progression after alectinib or ceritinib as first line therapy. Participants may have had prior chemotherapy, but only if before starting treatment with alectinib or ceritinib.
4. All Participants must have at least one measurable target extracranial lesion according to RECIST v1.1. Participants with asymptomatic CNS metastases will be eligible. The brain metastases may be newly diagnosed or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery. Participants who have leptomeningeal disease or carcinomatous meningitis will be eligible if the LM/CM is visualized on magnetic resonance imaging or if documented baseline cerebral spinal fluid positive cytology is available.
5. Eastern Cooperative Oncology Group Performance Status 0 or 1.
6. Adequate bone marrow functioning.
7. Adequate pancreatic function.
8. Adequate renal function.
9. Adequate liver function.
10. Acute effects of any prior therapy resolved to baseline severity or to CTCAE Grade =1 except for adverse events (AEs) that in the investigator’ judgment do not constitute a safety risk for the participant.
11. Systemic anti-cancer therapy with alectinib or ceritinib discontinued within a minimum of 5 half-lives prior to first dose of lorlatinib on the study.
12. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
1. Prior ALK TKI treatment or anti-cancer treatment other than first line alectinib or ceritinib.
2. Spinal cord compression.
3. Gastrointestinal abnormalities.
4. Active and clinically significant bacterial, fungal, or viral infection.
5. Clinically significant vascular and non-vascular cardiac conditions.
6. Participants presenting with abnormal Left Ventricular Ejection Fraction by echocardiogram or Multi-Gated Acquisition Scan according to institutional lower limits.
7. Participants with predisposing characteristics for acute pancreatitis according to investigator judgment.
8. History or known presence of interstitial fibrosis, interstitial lung disease, pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis.
9. Other severe acute or chronic medical or psychiatric condition.
10. Evidence of active malignancy.
11. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
12. Prior irradiation to >25% of the bone marrow.
13. 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: a. Known strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s Wort).
b. Known strong CYP3A inhibitors (eg, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], boceprevir, cobicistat, clarithromycin, conivaptan, diltiazem, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, paritaprevir and posaconazole, ritonavir, alone and with danoprevir or elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir, troleandomycin, and voriconazole, grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos]). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed. Note that strong CYP3A inhibitors can be stopped up to one day prior to first dose of lorlatinib on study. c. Known CYP3A substrates with narrow therapeutic index, such as astemizole*, terfenadine*, cisapride*, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) (*withdrawn from United States [US] market).
Known permeability glycoprotein (P-gp) substrates with a narrow therapeutic index (eg, digoxin).
14. Major surgery within 4 weeks prior to enrollment. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess Overall and Intracranial Response Rate of single-agent lorlatinib in participants with advanced ALK positive NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy;Secondary Objective: 1 To assess secondary measures of clinical efficacy<br>2 To confirm the safety and tolerability of lorlatinib;Primary end point(s): Confirmed Objective Tumor Response assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 per Independent Central Review (ICR);Timepoint(s) of evaluation of this end point: During the whole study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Every endpoint assessed by RECIST version 1.1<br>1. Confirmed ObjectiveTumor Response assessed by Investigator (INV)<br>2. Confirmed Intracranial tumor response assessed per ICR and INV <br>3. TTR per ICR and INV<br>4. DOR per ICR and INV<br>5. Duration of Intracranial response (IC-DOR) per ICR and INV<br>6. TTP per ICR and INV<br>7. PFS per ICR and INV<br>8. Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.03), seriousness, and relationship to study therpy;Timepoint(s) of evaluation of this end point: During the whole study