Trial Title:
Study of Bevacizumab in Combination With Chemoimmunotherapy and Atezolizumab in Patients With Extensive Stage Small Cell Lung Cancer and Liver Metastases
NCT ID:
NCT05588388
Condition:
Extensive-stage Small-cell Lung Cancer
Liver Metastases
Conditions: Official terms:
Lung Neoplasms
Neoplasm Metastasis
Small Cell Lung Carcinoma
Liver Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
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
Arm group label:
Experimental Treatment
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.
Detailed description:
This is a phase II, open-label, multicenter, single-arm study designed to evaluate the
efficacy and safety of bevacizumab plus atezolizumab plus carboplatin plus etoposide
(ABCE) followed by bevacizumab plus atezolizumab (AB) maintenance in Extensive-Stage
Small Cell Lung Cancer patients (ES-SCLC patients) with Liver Metastases (LM) who have
received no prior systemic treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of
contraception.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use a condom, and agreement to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential or pregnant female partner, men
must remain abstinent or use a condom during treatment with chemotherapy (i.e.,
carboplatin and etoposide) and for at least 6 months after the final dose of
chemotherapy, atezolizumab and bevacizumab to avoid exposing the embryo. Men
must refrain from donating sperm during this same period.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post-ovulation methods) and withdrawal are not adequate methods of preventing
drug exposure.
Exclusion Criteria:
- 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
- No occurrence of acute exacerbations of the underlying condition requiring psoralen
plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
calcineurin inhibitors, or high-potency or oral corticosteroids within the previous
12 months
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Active tuberculosis
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment, or anticipation of need for a major surgical
procedure during the study
- History of malignancy other than SCLC within 3 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death (e.g.,
5-year OS rate greater-than 90%), such as adequately treated carcinoma in situ of
the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma
in situ, or Stage I uterine cancer treated surgically with curative intent.
- Severe infection within 4 weeks prior to initiation of study treatment, including,
but not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment
o Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract
infection or chronic obstructive pulmonary disease exacerbation) are eligible for
the study.
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, or may render the patient at high risk
from treatment complications
- Known human immunodeficiency virus (HIV) infection. HIV-infected subjects on
effective anti-retroviral therapy are eligible if the most recent viral load test
performed within six months of screening (based on medical chart review) is
negative.
- Known chronic hepatitis B
- Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to
initiation of study treatment, during treatment with atezolizumab, and for 5 months
after the last dose of atezolizumab.
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNFα agents) within 2 weeks prior to initiation of study treatment, or
anticipation of 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
confirmation with the Principal Investigator has been obtained.
- Patients who received mineralocorticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or
low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency
are eligible for the study.
- History of severe allergic anaphylactic reactions to chimeric or humanized
antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
- Known allergy or hypersensitivity to any component of the bevacizumab formulation
- Currently taking or plan to take traditional herbal medicines.
- Treatment with investigational therapy within 28 days prior to initiation of study
treatment
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amy Oppenheim
Phone:
310-423-3713
Email:
Amy.Oppenheim@cshs.org
Investigator:
Last name:
Kamya Sankar, MD
Email:
Principal Investigator
Investigator:
Last name:
Sukhmani Padda, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ronald Natale, MD
Email:
Sub-Investigator
Investigator:
Last name:
Karen Reckamp, MD
Email:
Sub-Investigator
Facility:
Name:
V.A. Ann Arbor Healthcare System
Address:
City:
Ann Arbor
Zip:
48105
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Brittany Pannecouk, BS
Phone:
734-845-3966
Email:
Britanny.Pannecouk@va.gov
Contact backup:
Last name:
Melissa Robinson, MPH
Phone:
734-222-7474
Email:
Melissa.Robinson1@va.gov
Investigator:
Last name:
Nithya Ramnath, MBBS
Email:
Principal Investigator
Investigator:
Last name:
Garth W Strohbehn, MD
Email:
Sub-Investigator
Investigator:
Last name:
Michael D Green, MD PhD
Email:
Sub-Investigator
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Dominique Dippman
Email:
dippmand@med.umich.edu
Investigator:
Last name:
Angel Qin, MD
Email:
Principal Investigator
Investigator:
Last name:
Gregory P. Kalemkerian, MD
Email:
Sub-Investigator
Start date:
August 1, 2024
Completion date:
September 28, 2027
Lead sponsor:
Agency:
Kamya Sankar
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Collaborator:
Agency:
University of Michigan
Agency class:
Other
Collaborator:
Agency:
VA Ann Arbor Healthcare System
Agency class:
U.S. Fed
Source:
Cedars-Sinai Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05588388
