Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers

NCT03868423 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: OSU-17060NCI-2017-01394P30CA016058
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Malignant Neoplasm; ALK Fusion Protein Expression; ALK Gene Amplification; ALK Gene Mutation; Locally Advanced Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Neoplasm in the Central Nervous System; Metastatic Malignant Solid Neoplasm; ROS1 Fusion Positive; ROS1 Gene Amplification; ROS1 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Overall response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  Response for tumors will be assessed using the RECIST 1.1 criteria (using computed tomography scans or calipers by clinical exam) where response will be defined as a partial or complete response. Will be calculated with 95% binomial confidence intervals for the estimate of the proportion of responses.

  Up to 52 weeks

Secondary Outcomes (11)

• Confirmed objective response rate (ORR)

  Up to 52 weeks

• Time to response

  Up to 52 weeks

• Duration of response

  From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 52 weeks

• Time on treatment

  Up to 52 weeks

• Disease control rate

  Up to 52 weeks

Other Outcomes (2)

• Brigatinib exposure

  Up to 52 weeks

• Correlative gene and protein markers

  Up to 52 weeks

Study Arms (1)

Treatment (brigatinib)

EXPERIMENTAL

Patients receive brigatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Brigatinib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Brigatinib DRUG

90 mg orally QD for 7 days followed by 180 mg orally QD continuously thereafter. One cycle of therapy will consist of 28 days of treatment.

Also known as: Alunbrig, AP 26113, AP-26113, AP26113

Treatment (brigatinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (brigatinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (brigatinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (brigatinib)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors
• Patients must have activating genomic alterations in ALK or ROS1 (mutations, fusions or amplifications) by any validated Clinical Laboratory Improvement Act (CLIA)-certified molecular testing (fluorescence in situ hybridization \[FISH\], polymerase chain reaction \[PCR\] or next-generation sequencing \[NGS\] data are acceptable); CLIA validated results from other institutions and commercial diagnostic labs (e.g. Foundation Medicine) are also acceptable
• Patients with progressive disease on any previous therapy including crizotinib and other ALK tyrosine kinase inhibitors (TKIs), chemotherapy or immunotherapy
• Patients with locally advanced or metastatic solid tumors who have received no previous therapy of any kind (i.e. first-line therapy) are eligible
• Patients with brain metastases or metastases elsewhere within the central nervous system (CNS) are eligible for study; patients must be neurologically stable and asymptomatic
• Patients with tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure will have mandatory pre-treatment tumor biopsy or sampling; however, if patients do not have a tumor suitable for biopsy but have another tissue (preferably progressive metastatic site) available for molecular evaluation this will be acceptable
• Patients with solid tumors must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; Note: previously irradiated lesions may not be used for target lesions; unless there is unambiguous radiological progression after radiotherapy; brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Life expectancy of greater than 3 months
• Patients with multiple malignancies remain eligible
• Patients with an inherited cancer syndrome or a medical/family history suggestive of an inherited cancer syndrome remain eligible
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 4 months after the end of treatment; for women of childbearing potential, a negative pregnancy test must be documented prior to registration
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 10 g/dL
• Platelet count \>= 75,000/mcL

You may not qualify if:

• Patients with hematological malignancies
• Patients with ALK positive (+) lung cancer
• Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 30 days prior to registration on study
• Pregnant women or mothers who are breastfeeding
• Patients who are incarcerated
• Patients who have a history or the presence at baseline of pulmonary interstitial disease or drug-related pneumonitis, or radiation pneumonitis
• Patients who have a known history of human immunodeficiency virus (HIV); testing not required in the absence of history
• Patients with history of clinically significant bleeding disorder or history of active significant gastrointestinal (GI) bleeding within 3 months of first dose of brigatinib
• Patients who have malabsorption syndrome or other GI illness or condition that could affect oral absorption of the study drug
• History of allergic or suspected hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to brigatinib
• Patients with history of clinically significant atrial arrhythmias (requiring any anti-arrhythmic therapy or as determined by the treating physician) or any history of ventricular arrhythmias
• Patients who have significant, uncontrolled or active cardiovascular disease, including but not restricted to the following:
• Myocardial infarction (MI) within 6 months prior to first dose of brigatinib
• Unstable angina (UA) within 6 months prior to first use
• Decompensated congestive heart failure within 6 months prior to first dose

Sponsors & Collaborators

• Sameek Roychowdhury: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sameek Roychowdhury, MD

  Ohio State University Comprehensive Cancer Center

  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: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: March 11, 2019
• Study Start: March 20, 2019
• Primary Completion: November 20, 2020
• Study Completion: December 30, 2021
• Last Updated: February 18, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)