Study of Bevacizumab in Combination With Chemoimmunotherapy and Atezolizumab in Patients With Extensive Stage Small Cell Lung Cancer and Liver Metastases

NCT05588388 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT2022-05-Sankar-BELIEVE
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

This clinical trial aims to assess whether the addition of bevacizumab to atezolizumab and chemotherapy can improve response to treatment and progression-free survival in patients with extensive-stage small cell lung cancer (ES-SCLC) with liver metastases. The main questions it aims to answer are:

• In patients with ES-SCLC with liver metastases, can bevacizumab in combination with atezolizumab and chemotherapy prolong the length of time that the cancer does not progress?
• Is bevacizumab safe and tolerable when combined with atezolizumab and chemotherapy in patients with ES-SCLC and liver metastases? The study treatment includes two phases:
• Induction phase: bevacizumab will be administered in combination with atezolizumab and chemotherapy on a 21-day cycle for four cycles.
• Maintenance: atezolizumab and bevacizumab will be administered every 21 days for up to 12 months, or until unacceptable toxicity or disease progression. Participants will undergo blood tests every 3 weeks and tumor assessments every 6 weeks.

Conditions

Extensive-stage Small-cell Lung Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• 6- month Progression Free Survival (PFS) rate

  Proportion of patients with first occurrence of disease progression or death from any cause (whichever occurs first)

  Start of study treatment to 6-months

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  From time of first dose until death or the first occurrence of disease progression whichever occurs first, assessed up to approximately 48 months

• Overall Survival (OS)

  From time of first dose until death from any cause, assessed up to approximately 48 months

• Objective Response Rate

  From time of first dose until time of best (maximal) response, assessed up to approximately 48 months

• Incidence of adverse events

  From time of first dose until 90 days following the end of treatment, initiation of new systemic anti-cancer therapy, or death (whichever occurs first), assessed up to approximately 48 months

Other Outcomes (1)

• Tissue and blood based biomarkers

  From baseline to approximately 15 months

Study Arms (1)

Experimental Treatment

EXPERIMENTAL

1. Induction (ABCE): Atezolizumab 1200 mg, Bevacizumab 15 mg/kg, Carboplatin AUC5, Etoposide 100 mg/m2, given IV Q3weeks 2. Maintenance (AB): Atezolizumab 1200 mg and Bevacizumab 15 mg/kg given IV Q3weeks for 1 year, or until disease progression, or unacceptable toxicity

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Addition of Bevacizumab to current standard of care treatment (atezolizumab, carboplatin and etoposide) followed by maintenance Bevacizumab plus Atezolizumab for patients with ES-SCLC with LM

Experimental Treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability for subject to sign informed consent form and ability for subject to comply with the requirements of the study.
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group staging system), and radiographic confirmation of LM at diagnosis.
• Patients with history of EGFR mutant non-small cell lung cancer with histologically confirmed transformation to small cell lung cancer with presence of liver metastases, who are chemotherapy and immunotherapy naïve are eligible.
• No prior treatment for ES-SCLC. Note: patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least six months since the last chemotherapy, radiotherapy or chemoradiotherapy cycle prior to diagnosis of ES-SCLC
• Measurable disease per RECIST v1.1
• Asymptomatic patients with treated or untreated CNS lesions are eligible if there is no progression between completion of CNS-directed therapy and screening radiographic study, and the following criteria are met:
• Metastases are limited to the cerebellum or supratentorial region (i.e., no metastases to the midbrain, pons, or medulla).
• Presence of measurable disease outside the CNS per RECIST v1.1.
• No history of intracranial hemorrhage or spinal cord hemorrhage.
• No stereotactic radiotherapy or whole brain radiotherapy within 14 days prior to initiation of study treatment or neurosurgical resection within 28 days prior to initiation of study treatment.
• Concurrent therapy of corticosteroids ≤ 10 mg of oral prednisone or equivalent and/or anticonvulsant therapy at stable dose.
• ECOG Performance Status of 0-2.
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula)
• ANC ≥1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support

You may not qualify if:

• History of leptomeningeal disease
• History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to first dose of protocol therapy.
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Anti-hypertensive therapy to achieve these parameters is allowable.
• Evidence of tumor invading or abutting major blood vessels.
• Prior history of hypertensive crisis or encephalopathy
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
• History of hemoptysis (≥one-half teaspoon of bright red blood per episode) within 1 month prior to study enrollment
• Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
• Current or recent (within 10 days of study enrollment) use of aspirin (\> 325 mg/day) or treatment with dipyramidole, ticlodipine, clopidogrel, and clostazol
• Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for \> 2 weeks prior to study enrollment
• The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks prior to enrollment.
• Prophylactic anticoagulation for the patency of venous access devices is allowed, provided the activity of the agent results in an INR\< 1.5 ×ULN and aPTT is within normal limits within 14 days prior to randomization. Prophylactic use of low-molecular-weight heparin (i.e., enoxaparin 40 mg/day) is permitted.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab
• History of abdominal or tracheosphageal fistula or gastrointestinal perforation within 6 months prior to study enrollment

Sponsors & Collaborators

• Kamya Sankar: lead
• Genentech, Inc.: collaborator
• University of Michigan: collaborator
• VA Ann Arbor Healthcare System: collaborator

Study Sites (3)

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

RECRUITING

V.A. Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract 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

• Kamya Sankar, MD

  Cedars-Sinai Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Oppenheim

CONTACT

310-423-3713; Amy.Oppenheim@cshs.org

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: Sponsor-Investigator

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 20, 2022
• Study Start: August 11, 2024
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): December 28, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)