- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02521051
Phase I/II Trial of Alectinib and Bevacizumab in Patients With Advanced, Anaplastic Lymphoma Kinase (ALK)-Positive, Non-Small Cell Lung Cancer
A Phase I/II Trial to Evaluate the Safety and Tolerability of Alectinib and Bevacizumab in Patients With Advanced, ALK-Positive, Non-Small Cell Lung Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase I/II clinical trial.
- A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose(s) of the investigational intervention to use for further studies.
- Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease.
"Investigational" means that the intervention is being studied.
- In this research study, the investigators are investigating the combination of two study drugs: alectinib and bevacizumab. The FDA (the U.S. Food and Drug Administration) has not approved alectinib as a treatment for any disease.
It has been found that some people with NSCLC have a change (mutation) in a certain gene called the anaplastic lymphoma receptor tyrosine kinase (ALK) gene. This mutated gene helps cancer cells grow.
-- Alectinib belongs to a class of drugs designed to inhibit ALK. This drug has been used in other research studies. Information from those other research studies suggests that alectinib may be effective in killing cancer cells that have changes in ALK. Only participants with changes in the ALK gene will be allowed to participate in this study.
In this research study, Alectinib will be combined with Bevacizumab.
-- Bevacizumab (also called Avastin) works by slowing or stopping the growth of cells in cancer tumors by decreasing the blood supply of the tumors. If blood supply is decreased, oxygen and nutrients that are needed for tumor growth are decreased. The FDA has approved Bevacizumab as a treatment option for your disease
The purpose of this study is to test the safety of Alectinib and Bevacizumab. The investigators will also determine how effective this combination is in participants with advanced, ALK-positive NSCLC with a focus on participants with brain metastases.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Justin Gainor, MD
- Phone Number: 617-724-4000
- Email: jgainor@partners.org
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Recruiting
- Massachusetts General Hospital
-
Contact:
- Justin L. Gainor, MD
- Phone Number: 617-724-4000
- Email: jgainor@partners.org
-
Principal Investigator:
- Justin Gainor, MD
-
Boston, Massachusetts, United States, 02155
- Recruiting
- Beth Israel Deaconess Medical Center
-
Contact:
- Daniel Costa, MD, PhD, MMSc
- Phone Number: 617-667-9236
- Email: dbcosta@bidmc.harvard.edu
-
Principal Investigator:
- Daniel Costa, MD, PhD, MMSc
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed advanced, non-squamous, non-small cell lung cancer.
- Molecular confirmation of an ALK rearrangement.
- Age ≥ 18 years old.
- Life expectancy > 12 weeks.
- Performance status 0-2.
- Adequate hematologic function:
Adequate renal function:
- An estimated Glomerular Filtration Rate (eGFR) of at least 45 mL/min/1.73 m2
- International normalized ration (INR)≤ 1.5
- Partial thromboplastin time (PTT) ≤1.5 x upper limit of normal (ULN)
- For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment.
- Able and willing to provide written informed consent
- Phase II Only:
Presence of at least one measurable central nervous system (CNS) target lesion (At least 5 mm in size)
- Lesions must be untreated or progressive according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after previous local therapy.
- Participants who are receiving corticosteroids must be on a stable or decreasing dose
- At least one measurable extra-CNS lesion based upon RECIST version 1.1.
Exclusion Criteria:
- Squamous cell histology or mixed, predominantly squamous adenosquamous carcinoma
- Previous history of haemoptysis
- Tumour infiltrating into large vessels or infiltrating into the proximal tracheobronchial network
- Unstable, symptomatic brain metastases.
- History of hemorrhagic CNS metastases
- History of intracranial hemorrhage (either by clinical history or neuroimaging)
- History of or genetic predisposition to a bleeding diathesis or coagulopathy
- Therapeutic anticoagulation
- Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (> 325 mg/day)
- Clinically significant heart disease (i.e., active), stroke or myocardial infarction within 6 months prior to enrolment, unstable angina pectoris, congestive heart failure of grade > II according to the New York Heart Association (NYHA), or cardiac arrhythmia requiring specific treatment
- Arterial or venous thromboembolic events within 6 months of study enrollment.
- Poorly controlled arterial hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
- Invasive surgical intervention within 28 days prior to the start of treatment
- Minor surgical intervention, including placement of a permanent catheter within 24 hours prior to the first infusion of bevacizumab.
- Non-healing wound, active peptic ulcer or bone fracture.
- Previous history of abdominal fistula, tracheoesophageal fistula or other fistula with grade 4 severity, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrolment.
- Proteinuria at baseline.
- Previous anti-angiogenic treatment
- Patients previously treated with alectinib (Phase II only).
- Radical radiotherapy to the thorax with curative intent within 28 days
- Cytotoxic chemotherapy within 21 days prior to enrolment.
- Treatment with crizotinib within 7 days prior to enrolment. For all other ALK Tyrosine kinase inhibitors (TKIs), the washout period should be ≥5 half-lives prior to enrolment.
- Any GI disorder that may affect absorption of oral medications
- Alanine transaminase (ALT) or aspartate transaminase (AST) > 3 × ULN (≥5 × ULN for patients with concurrent liver metastasis)
- Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
- Acute viral or active autoimmune, alcoholic, or other types of hepatitis
- National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g. radiotherapy) (excluding alopecia),
- History of organ transplant.
- Co-administration of anti-cancer therapies other than those administered in this study.
- QTc > 470 ms or patients with symptomatic bradycardia.
- Administration of strong/potent cytochrome P450 (CYP)3A inhibitors or inducers within 14 days
- Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drug and while on treatment.
- History of hypersensitivity to any of the additives in the alectinib drug formulation
- Documented allergy or hypersensitivity to monoclonal antibodies (bevacizumab)
- History of drug-induced pneumonitis or hypersensitivity pneumonitis from prior ALK TKI therapy.
- Pregnant or lactating women.
- Known HIV positivity or AIDS-related illness.
- Any condition or illness that could compromise patient safety or interfere with the evaluation of the study drugs.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Alectinib and Bevacizumab.
Phase 1
Phase II In the phase II portion of this study, the investigators will evaluate the combination of alectinib plus bevacizumab in ALK-positive patients with untreated or progressive, asymptomatic brain metastases. Eligible participants will receive alectinib plus bevacizumab at the recommended phase II doses determined in the phase I portion of the study. |
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended phase II dose of the combination of Alectinib and Bevacizumab
Time Frame: 21 Days
|
Phase I Primary Endpoint: To determine the recommended phase II dose of the combination of alectinib and bevacizumab.
|
21 Days
|
Number of participants treated with the combination of alectinib and bevacizumab with adverse events
Time Frame: 2 years
|
Phase II Primary Endpoint: Safety and tolerability of alectinib and bevacizumab as assessed by Common Terminology Criteria for Adverse Events version 4.0
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Central nervous system objective response rate
Time Frame: 2 years
|
Number of subjects with intracranial complete or partial responses
|
2 years
|
Central nervous system disease control rate
Time Frame: 2 years
|
Number of subjects with intracranial complete responses, partial responses, or stable disease
|
2 years
|
Central nervous system progression-free survival
Time Frame: 2 years
|
Time from initiation of alectinib/bevacizumab to central nervous system progression or death.
|
2 years
|
Overall objective response rate
Time Frame: 2 years
|
Number of subjects with partial or complete responses
|
2 years
|
Overall disease control rate
Time Frame: 2 years
|
Number of subjects with partial/complete responses or stable disease
|
2 years
|
Progression-free survival
Time Frame: 2 years
|
Time from initiation of alectinib/bevacizumab to progression or death.
|
2 years
|
Quality of life: change from baseline to on-treatment, measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30
Time Frame: 2 years
|
Questionnaire
|
2 years
|
Quality of life: change from baseline and on-treatment, measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-BN20
Time Frame: 2 years
|
Questionnaire
|
2 years
|
Number of patients with an ALK resistance mutation
Time Frame: 2 years
|
Determination of the number of patients who develop an ALK resistance mutation as a mechanism of resistance to alectinib and bevacizumab
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Justin Gainor, MD, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- 15-055
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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