Phase I/II Trial of Alectinib and Bevacizumab in Patients With Advanced, Anaplastic Lymphoma Kinase (ALK)-Positive, Non-Small Cell Lung Cancer

NCT02521051 | Terminated Phase 1 Results DMC

• 1 other identifier: 15-055
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating two drugs, alectinib and bevacizumab, as possible treatments for Advanced Non-Small Cell Lung Cancer (NSCLC).

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Keywords

Non-Small Cell Lung Cancer (NSCLC); Anaplastic lymphoma kinase; ALK; Brain metastases

Outcome Measures

Primary Outcomes (3)

• (Phase 1) Recommended Phase II Dose of Alectinib

  The recommended phase II doses for the combination of alectinib and bevacizumab will be defined as either a) the highest dosage cohort in which less than 1/3 of patients experience a dose-limiting toxicity or b) alectinib at the previously defined recommended phase II dose (600 mg twice daily PO) as a single agent plus bevacizumab at the highest tolerated dose (15 mg/kg IV every 21 days) investigated in this indication - whichever is the lower dose. Dose-limiting toxicities (DLTs) were defined as adverse events (AEs) occurring within the first cycle of treatment (21 days) attributed to the study drugs.

  first cycle of treatment (21 days)

• (Phase 1) Recommended Phase II Dose of Bevacizumab

  The recommended phase II doses for the combination of alectinib and bevacizumab will be defined as either a) the highest dosage cohort in which less than 1/3 of patients experience a dose-limiting toxicity or b) alectinib at the previously defined recommended phase II dose (600 mg twice daily PO) as a single agent plus bevacizumab at the highest tolerated dose (15 mg/kg IV every 21 days) investigated in this indication - whichever is the lower dose. Dose-limiting toxicities (DLTs) were defined as adverse events (AEs) occurring within the first cycle of treatment (21 days) attributed to the study drugs.

  first cycle of treatment (21 days)

• (Phase 2) Number of Participants With Intracranial Hemorrhagic Events Who Received RP2D

  In the phase II portion of the study, we aim to further investigate the safety and tolerability of alectinib plus bevacizumab at the RP2Ds as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The combination of alectinib and bevacizumab will be deemed unsafe if 2 or more participants are observed to have grade 2 or higher, central nervous system (CNS) intracranial hemorrhagic events.

  up to 4 years

Secondary Outcomes (8)

• Central Nervous System Objective Response Rate

  Up to 4 years

• Central Nervous System Disease Control Rate

  Up to 4 years

• Central Nervous System Progression-free Survival

  up to 4 years

• Overall Objective Response Rate

  Up to 4 years

• Overall Disease Control Rate

  Up to 4 years

Study Arms (4)

Phase I Dose Level 1: Alectinib 600 mg + Bevacizumab 15 mg/kg

EXPERIMENTAL

Participants were administered Alectinib 600 mg twice daily by mouth, and Bevacizumab 15 mg/kg intravenously once every 3 weeks. DLTs will be monitored and evaluated throughout the first cycle (21 days).

Drug: Alectinib; Drug: Bevacizumab

Phase I Dose Level -1: Alectinib 600 mg + Bevacizumab 7.5 mg/kg

EXPERIMENTAL

Participants were administered Alectinib 600 mg twice daily by mouth, and Bevacizumab 7.5 mg/kg intravenously once every 3 weeks. DLTs will be monitored and evaluated throughout the first cycle (21 days).

Drug: Alectinib; Drug: Bevacizumab

Phase I Dose Level -2: Alectinib 450 mg + Bevacizumab 7.5 mg/kg

EXPERIMENTAL

Participants were administered Alectinib 450 mg twice daily by mouth, and Bevacizumab 7.5 mg/kg intravenously once every 3 weeks. DLTs will be monitored and evaluated throughout the first cycle (21 days).

Drug: Alectinib; Drug: Bevacizumab

Phase II: RP2D

EXPERIMENTAL

In the phase II portion of the study, all patients received alectinib plus bevacizumab at the RP2D determined in the phase I portion.

Drug: Alectinib; Drug: Bevacizumab

Interventions

Alectinib DRUG

Also known as: Alecensa

Phase I Dose Level -1: Alectinib 600 mg + Bevacizumab 7.5 mg/kg; Phase I Dose Level -2: Alectinib 450 mg + Bevacizumab 7.5 mg/kg; Phase I Dose Level 1: Alectinib 600 mg + Bevacizumab 15 mg/kg; Phase II: RP2D

Bevacizumab DRUG

Also known as: Avastin

Phase I Dose Level -1: Alectinib 600 mg + Bevacizumab 7.5 mg/kg; Phase I Dose Level -2: Alectinib 450 mg + Bevacizumab 7.5 mg/kg; Phase I Dose Level 1: Alectinib 600 mg + Bevacizumab 15 mg/kg; Phase II: RP2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

alectinib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was stopped prematurely because of slow accrual, leasing to small numbers of subjects analyzed.

Results Point of Contact

• Title: Justin Gainor, MD
• Organization: Massachusetts General Hospital

jgainor@partners.org

617-724-4000

Study Officials

• Justin Gainor, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: August 13, 2015
• Study Start: September 28, 2015
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: May 13, 2025
• Results First Posted: May 13, 2025

Record last verified: 2025-04

Locations

US (1)