Phase Ib Trial of Infigratinib In Combination With Atezolizumab And Bevacizumab for The Second-Line Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion/Amplification

NCT05510427 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0149NCI-2022-06868
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To find the highest tolerable dose of infigratinib that can be given in combination with bevacizumab and atezolizumab to patients with advanced/metastatic CCA with a FGFR2 mutation.

Conditions

Cholangiocarcinoma; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (2)

Part A (Dose Escalation)

EXPERIMENTAL

The first group of participants will receive the lowest dose level of infigratinib.

Drug: Infigratinib; Drug: Atezolizumab; Drug: Bevacizumab

Part B (Dose Expansion)

EXPERIMENTAL

Participants will receive infigratinib at the recommended dose that was found in Part A.

Drug: Infigratinib; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Infigratinib DRUG

Given by PO

Part A (Dose Escalation); Part B (Dose Expansion)

Atezolizumab DRUG

Given by (IV) vein

Part A (Dose Escalation); Part B (Dose Expansion)

Bevacizumab DRUG

Given by (IV) vein

Part A (Dose Escalation); Part B (Dose Expansion)

Eligibility Criteria

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

You may qualify if:

• Is male or female aged ≥18 years.
• Has histologically confirmed metastatic or advanced unresectable cholangiocarcinoma.
• Has disease that is measurable per the RECIST v1.1.
• Has FGFR2 fusion in tumor tissue. Presence of the FGFR2 fusion should be determined by CLIA-validated genomic testing of a tumor tissue specimen (DNA-based or RNA-based).
• Is refractory to, has demonstrated intolerance to, or has refused access to, available standard therapies. Refractory patients should have evidence of progressive disease on at least one prior standard chemotherapy regimen for advanced or metastatic disease. Patients who discontinued available standard therapy due to toxicity must have continued evidence of measurable disease.
• Has archival formalin-fixed, paraffin-embedded primary tumor tissue available or patient is willing to undergo a pretreatment biopsy.
• Is able to take oral medication.
• Is able to comply with protocol procedures and scheduled visits.
• Has Eastern Cooperative Oncology Group performance status of 0 or 1
• Has adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1000/µL) without granulocyte colony-stimulating factor support
• Platelet count ≥ 75 × 109/L (75,000/µL) without transfusion
• Hemoglobin ≥ 80 g/L (8 g/dL) i. Patients may be transfused to meet this criterion.
• Aspartate amino transferate (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following exceptions: i. Patients with documented liver metastases: AST and ALT
• × ULN ii. Patients with documented liver or bone metastases: ALP

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Patients with untreated CNS metastases are excluded from study
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease.
• If the patient is receiving anti-convulsant therapy, the dose is considered stable. IF BRAIN SCANS are not done: Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS directed therapy and initiation of study treatment.
• Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy and/or surgery, with no need to repeat the screening brain scan.
• Received treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, or anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipates a need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• Received chemotherapy, biologic therapy, immunotherapy, or investigational agent within 4 weeks prior to enrollment.
• Received treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Helsinn Healthcare SA: collaborator

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Cholangiocarcinoma; Liver Neoplasms

Interventions

infigratinib; atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sunyoung Lee, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 22, 2022
• Study Start: August 7, 2023
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: August 15, 2023

Record last verified: 2023-08