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

Recruiting now · Phase 2

Conditions studied: Extensive-stage Small-cell Lung Cancer, Liver Metastases

In brief

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.

Key facts

Study ID

NCT05588388

Run by

Kamya Sankar

People needed

39

Starts

2024-08-11

Expected to finish

2027-12-28

Last updated by the study team

2025-11-17

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

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
• Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion
• AST, ALT, and alkaline phosphatase (ALP) ≤ 5 x upper limit of normal (ULN), and serum bilirubin ≤ 1.5 x ULN
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• For patients who have positive hepatitis C antibody, HCV RNA must be performed at screening. For patients with a positive hepatitis C antibody with prior treatment or natural resolution who have negative HCV RNA are eligible. Patients with untreated hepatitis C may enroll if hepatitis is stable, and the patient is not at risk for hepatic decompensation. For those on concurrent HCV treatment, the HCV RNA level should be below the limit of quantification.
• Negative serum pregnancy test for women of childbearing potential.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, as defined below:
• Women must remain abstinent or use an acceptable contraceptive method during the treatment period and for 5 months after the final dose of atezolizumab and 6 months after the final dose of bevacizumab.
• A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
• Examples of acceptable contraceptive methods include, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

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
• Clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection All patients with ≥ 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (refer to Appendix 12.5 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with rheumatoid arthritis who are on a stable pain regimen with symptom control.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all following conditions are met:
• Rash must cover > 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids

Where it is running

• Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute — Los Angeles, California, United States (enrolling)
• V.A. Ann Arbor Healthcare System — Ann Arbor, Michigan, United States (enrolling)
• University of Michigan — Ann Arbor, Michigan, United States (enrolling)

Full record on ClinicalTrials.gov

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