Vorolanib + Atezolizumab as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer
Condition: Extensive-stage Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Vorolanib; Atezolizumab
Intervention description: Vorolanib is administered orally at a dose of 200 mg on Days 1 through 21 of each 21-day cycle.; Atezolizumab is administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.
Intervention MeSH terms: Atezolizumab; Vorolanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Extensive stage small cell lung cancer

Summary:

      The purpose of the study is to determine whether adding vorolanib to atezolizumab will
      improve the length of time that participants are cancer-free after receiving standard
      chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed extensive stage small cell lung cancer
             without prior specific systemic therapy aside from induction with platinum, etoposide,
             and atezolizumab. Measurable disease is not required for eligibility.

          -  Receipt of at least 3 cycles (and no more than 4 cycles) of platinum plus etoposide
             and atezolizumab during the induction phase, without tumor progression as determined
             by CT scan and brain MRI. Patients should be able to start the study treatment no more
             than 6 weeks from the last dose of induction chemo/immunotherapy. This period may be
             extended to 8 weeks in patients requiring brain radiotherapy after completion of
             induction chemo/immunotherapy for brain metastases.

          -  At least 18 years of age.

          -  ECOG performance status ≤ 1

          -  Normal bone marrow and organ function as defined below:

               -  Absolute neutrophil count ≥ 1.5 K/cumm

               -  Platelets ≥ 100 K/cumm

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total bilirubin ≤ 1.5 x IULN

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (≤ 5 x IULN for patients with liver metastases)

               -  Creatinine ≤ 1.5 x IULN OR measured or calculated creatinine clearance > 50
                  mL/min for patients with creatinine levels > 1.5 x IULN

               -  Urine protein ≤ 1+ or urine protein to creatinine ratio ≤ 1; if UPC ratio is > 1
                  on urinalysis, then 24-hour urine collection for protein must be obtained and
                  level must be < 1,000 mg for patient enrollment

               -  aPTT and either INR or PT ≤ 1.5 x IULN unless participant is receiving
                  anticoagulant therapy as long as PT or a PTT is within therapeutic range of
                  intended use of anticoagulants.

          -  Patients receiving therapeutic non-Coumadin anticoagulation are eligible, provided
             they are on a stable dose (per investigator judgment) of anticoagulant.

          -  The effects of atezolizumab and vorolanib on the developing human fetus are unknown.
             For this reason, women of childbearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control, abstinence) prior to study
             entry and for the duration of study participation. Should a woman become pregnant or
             suspect she is pregnant while participating in this study, she must inform her
             treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of the study,
             and 31 weeks after last dose of study treatment. Women must use birth control for at
             least 31 weeks after last dose of study treatment. Women must not be breastfeeding.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria

          -  A history of other malignancy with the exception of malignancies for which all
             treatment was completed at least 2 years before registration and the patient has no
             evidence of disease.

          -  Currently receiving any other investigational agents.

          -  Patients with untreated brain metastases are excluded. Patients with clinically
             evident CNS hemorrhage are excluded. Prophylactic cranial irradiation is not allowed.
             Patients with brain metastases treated with whole brain radiation therapy,
             radiosurgery, or surgery are eligible.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to vorolanib, atezolizumab, or other agents used in the study.

          -  Use of chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory
             drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or
             clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is
             permitted.

          -  Systemic glucocorticoids with prednisone dose higher than 10 mg/day or equivalent.

          -  Arterial or venous thromboembolic event, including but not limited to myocardial
             infarction, transient ischemic attack, cerebrovascular accident, or unstable angina,
             within 6 months prior to enrollment.

          -  Uncontrolled or poorly controlled hypertension with systolic blood pressure (BP)> 160
             mmHg systolic or diastolic > 100 mmHg for > 3 weeks prior to C1D1), despite standard
             medical management.

          -  Gastrointestinal perforation, and/or fistula, or risk factors for perforation within 6
             months prior to enrollment.

          -  Grade 3 or 4 gastrointestinal bleeding within 3 months prior to enrollment.

          -  History of active autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
             glomerulonephritis.

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.

          -  Hemoptysis (defined as bright red blood or ≥ ½ teaspoon) within 28 days prior to Cycle
             1 Day 1 or with radiographic evidence of intratumor cavitation or radiologically
             documented evidence of major blood vessel invasion or encasement by cancer.

          -  Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to Cycle 1
             Day 1.

          -  Undergone major surgery within 28 days prior to Cycle 1 Day 1, or minor
             surgery/subcutaneous venous access device placement within 7 days prior to Cycle 1 Day
             1, or has elective or planned major surgery to be performed during the course of the
             clinical trial.

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis, cirrhosis at a level of Child-Pugh B or worse, cirrhosis (any degree)
             with a history of hepatic encephalopathy or clinically meaningful ascites resulting
             from cirrhosis (defined as ascites from cirrhosis requiring diuretics or
             paracentesis), fatty liver, and inherited liver disease.

          -  Active tuberculosis.

          -  Administration of a live, attenuated influenza vaccine within 4 weeks before Cycle 1
             Day 1 or at any time during the study.

          -  Severe infections within 2 weeks prior to Cycle 1 Day 1, including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia.

          -  Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1 Day 1.
             Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary
             tract infection or chronic obstructive pulmonary disease) are eligible.

          -  History of deep venous thrombosis, pulmonary embolism, or any other significant
             thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis
             are not considered "significant") during the 3 months prior to Cycle 1 Day 1.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             serum pregnancy test within 7 days prior to C1D1.

          -  Active hepatitis B (chronic or acute) defined as having a positive hepatitis B surface
             antigen (HBsAg) test at screening. Note: Patients with past or resolved hepatitis B
             infection (defined as having a negative HBsAg test and a positive total hepatitis B
             core antibody (HBcAb) test are eligible.

          -  Patients known to be HIV positive are ineligible.