Alectinib in Combination With Bevacizumab in ALK Positive NSCLC

NCT03779191 | Completed Phase 2 FDA Drug

• 1 other identifier: Alectinib plus Bevacizumab
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm, open-label, phase II clinical study aims to evaluate the progression-Free Survival (PFS) of the combination of Alectinib plus Bevacizumab in untreated and first and second-line chemotherapy failed subjects with stage IIIB/IV or recurrent disease after receiving radiation therapy or surgical resection. The main question to be answered is: Whether the combination of Alectinib plus Bevacizumab will improve PFS in untreated and previously treated subjects with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) and positive ALK translocation. Participants will be treated with Alectinib and Bevacizumab every three weeks until disease progression, unacceptable toxicity, or patient withdrawal of consent.

Conditions

ALK Gene Rearrangement Positive; Non-Squamous Non-Small Cell Neoplasm of Lung

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS based on response criteria according to RECIST 1.1 in untreated and previously treated patients with Advanced or metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab

  Through study completion, an average of 18 months

Secondary Outcomes (7)

• Objective response rate

  8 weeks

• Brain- ORR

  8 weeks

• Overall survival

  Through study completion, an average of 18 months

• Time to developing brain metastases

  Through study completion, an average of 18 months

• Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment

  From Baseline up to Cycle 20 (each cycle is 3 weeks) Day 1.

Study Arms (1)

Intervention

EXPERIMENTAL

Patients in this intervention arm will receive the therapeutic combination of Alectinib dosed PO 600 mg bis in die (BID) with meals and Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Drug: Alectinib; Drug: Bevacizumab

Interventions

Alectinib DRUG

Alectinib dosed 600 mg twice a day (BID) with meals until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Also known as: Alecensa

Intervention

Bevacizumab DRUG

Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Also known as: Avastin

Intervention

Eligibility Criteria

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

You may qualify if:

• Men and women, ≥18 years of age.
• Subjects with NSCLC with known ALK-rearrangement tested with FDA-approved test (IHQ or FISH).
• Subjects with sufficient tissue to test for ALK-rearranged using IHQ or FISH.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Karnofsky Performance Status of ≥70
• Subjects with histologically confirmed Stage 3B (IIIB), 4 (IV) or recurrent NSCLC (per the 8th International Association for the Study of Lung Cancer classification, non-squamous histology, with prior systemic chemotherapy (platinum-based) given as primary therapy for advanced disease. Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration of the prior regimen occurred at least 3 weeks prior to enrollment. Prior treatment with ALK inhibitors is permitted as long as the last administration occurred 3 weeks prior to enrollment.
• Subjects with CNS metastases are only eligible if the CNS metastases are adequately treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 1 week prior to randomization.
• Patients receiving radiotherapy or radiosurgery with a dose exceeding 30 Gy will have 3 weeks for neurological stabilization before randomization.
• This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Measurable disease by CT as per RECIST 1.1 criteria.
• a. The target lesions may be located on a previously irradiated field exists if documented progression of disease (radiographic) in that site.
• At least 12 weeks of life expectancy.
• Signed written informed consent
• Patients should have a signed and dated form of written informed consent approved by the institutional committee in accordance with regulatory and institutional guidelines. This must be obtained before performing any procedure related to the protocol that are not part of the normal care of the patient.
• Patients must be willing and able to comply with scheduled visits, treatment program, laboratory testing including filling of questionnaires the results reported by the patient and other study requirements.

You may not qualify if:

• Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested locally for EGFR mutation status; use of an FDA-approved test is strongly encouraged (EGFR mutation testing may be performed during the Screening Period, Non-squamous subjects with unknown or indeterminate EGFR status may not be included).
• Subjects with untreated CNS metastases are excluded.
• Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as Vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial
• Radiographical evidence of cavitated or necrotic tumors
• Centrally located tumors with radiographical evidence (CT or MRI) of local invasion of major blood vessels
• History of clinically significant hemoptysis within the past 3 months
• History of major thrombotic or clinically relevant major bleeding event in the past 6 months.
• Known inherited predisposition to bleeding or thrombosis
• Medical History and Concurrent Diseases
• Any medical condition or serious uncontrolled or active infection with hepatitis or HIV that could be reactivated.
• Other concurrent malignancies requiring intervention.
• All toxicities attributed to a previous treatment for cancer other than alopecia or fatigue, must have resolved to Grade 1 (NCI CTCAE version 4) or baseline, prior to administration of study drug.
• Prior treatment with tumor vaccines or other anti-tumor immune stimulating agents.

Sponsors & Collaborators

• Instituto Nacional de Cancerologia de Mexico: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Instituto Nacional de Cancerologia

Mexico City, 14080, Mexico

Location

Related Publications (9)

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MeSH Terms

Interventions

alectinib; Bevacizumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Oscar G Arrieta Rodriguez, M.D., M.Sc.

  Instituto Nacional de Cancerología de México

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinator of the Thoracic Oncology Unit and Laboratory of Personalized Medicine

Model Details: Phase II, single arm trial assessing Alectinib in combination with Bevacizumab in untreated and previously treated patients with Advanced or Metastatic Non-Squamous ALK-rearranged NSCLC

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: December 19, 2018
• Study Start: April 8, 2020
• Primary Completion: August 1, 2022
• Study Completion: October 30, 2022
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)