Clinical Trials /

Vorolanib + Atezolizumab as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer

NCT04373369

Description:

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.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vorolanib + Atezolizumab as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer
  • Official Title: A Phase II Study of Maintenance Vorolanib and Atezolizumab in Patients With Extensive-stage SCLC

Clinical Trial IDs

  • ORG STUDY ID: 20-X043
  • NCT ID: NCT04373369

Conditions

  • Extensive-stage Small Cell Lung Cancer

Interventions

DrugSynonymsArms
VorolanibX-82Vorolanib + Atezolizumab
AtezolizumabTecentriqVorolanib + Atezolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Vorolanib + AtezolizumabExperimentalConsenting and eligible participants who have no evidence of tumor progression after 3 to 4 cycles of standard-of-care induction therapy will receive atezolizumab intravenously (IV) every 3 weeks and vorolanib by mouth daily. Participants can continue to receive treatment up to two years.
  • Vorolanib
  • Atezolizumab

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 (see Appendix A)

          -  Normal bone marrow and organ function as defined below:

               -  Absolute neutrophil count ≥ 1,500 K/cumm

               -  Platelets ≥ 100,000 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival at 6 months
Time Frame:6 months
Safety Issue:
Description:Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study.) In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.) Kaplan-Meier product limit estimator will be used to estimate progression-free survival (PFS) at 6 months, with the inclusion of 90% confidence interval.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 3 years post start of treatment (up to 5 years)
Safety Issue:
Description:Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Subjects lost to follow-up will be excluded from the analysis. Progressive disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study.) In addition to he relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)
Measure:Overall survival
Time Frame:Up to 3 years post start of treatment (up to 5 years)
Safety Issue:
Description:Overall survival is defined as the length of time from the start of study treatment that patients diagnosed with the disease are still alive. Kaplan-Meier product limit estimator will be used to estimate the overall survival rate.
Measure:Safety and tolerability of treatment regimen as measured by the frequency of adverse events
Time Frame:From the start of treatment until 30 days after completion of treatment (up to 25 months).
Safety Issue:
Description:The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Trial Keywords

  • Extensive stage small cell lung cancer

Last Updated

April 30, 2020