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

Recruiting

Sponsor: Massachusetts General Hospital

Collaborators: Genentech, Inc.

Information provided by (Responsible party): Principal Investigator Massachusetts General Hospital Justin Gainor, MD Principal Investigator

ClinicalTrials.gov Identifier: NCT02521051

Protocol Info

Short Description: Phase I/II Trial to Evaluate Alectinib and Bevacizumab in NSLC
Long Description: 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
MGH Status: Open
Sponsor: DF/HCC
Disease Program: Thoracic

Next Steps


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Purpose

This research study is evaluating two drugs, alectinib and bevacizumab, as possible treatments for Advanced Non-Small Cell Lung Cancer (NSCLC).
Condition Title Intervention Phase
Non-Small Cell Lung Cancer (NSCLC) Alectinib Bevacizumab Phase 1/Phase 2
Study Type Interventional
Official Title 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

Primary Outcome Measures

Recommended phase II dose of the combination of Alectinib and Bevacizumab [Time Frame: 21 Days] [Designated as safety issue: ]

Number of participants treated with the combination of alectinib and bevacizumab with adverse events [Time Frame: 2 years] [Designated as safety issue: ]


Secondary Outcome Measures

Central nervous system objective response rate [Time Frame: 2 years] [Designated as safety issue: ]

Central nervous system disease control rate [Time Frame: 2 years] [Designated as safety issue: ]

Central nervous system progression-free survival [Time Frame: 2 years] [Designated as safety issue: ]

Overall objective response rate [Time Frame: 2 years] [Designated as safety issue: ]

Overall disease control rate [Time Frame: 2 years] [Designated as safety issue: ]

Progression-free survival [Time Frame: 2 years] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Number of patients with an ALK resistance mutation [Time Frame: 2 years] [Designated as safety issue: ]

Estimated Enrollment: 43
Study Start Date: October 2015
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: October 2019
Arms Assigned Interventions

Experimental:Alectinib and Bevacizumab.

Phase 1 Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Alectinib, orally, twice a day, per cycle Bevacizumab, iv, once per cycle 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.
Drug:Bevacizumab

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02521051

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02115
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02155

Sponsors and Collaborators

Massachusetts General Hospital

Genentech, Inc.

More Information

No publications provided

Responsible Party: Principal Investigator Massachusetts General Hospital Justin Gainor, MD Principal Investigator
ClinicalTrials.gov Identifier: NCT02521051
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Massachusetts General Hospital:

Non-Small Cell Lung Cancer (NSCLC)

Anaplastic lymphoma kinase

ALK

Brain metastases

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Bevacizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019