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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT04373369
Collaborator
Xcovery Holding Company, LLC (Industry)
33
Enrollment
1
Location
1
Arm
60.8
Anticipated Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Maintenance Vorolanib and Atezolizumab in Patients With Extensive-stage SCLC
Actual Study Start Date :
Oct 7, 2020
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Oct 31, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Vorolanib + Atezolizumab

Consenting 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.

Drug: Vorolanib
Vorolanib is administered orally at a dose of 200 mg on Days 1 through 21 of each 21-day cycle.
Other Names:
  • X-82
  • Drug: Atezolizumab
    Atezolizumab is administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.
    Other Names:
  • Tecentriq
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival at 6 months [6 months]

      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

    1. Progression-free survival [Up to 3 years post start of treatment (up to 5 years)]

      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.)

    2. Overall survival [Up to 3 years post start of treatment (up to 5 years)]

      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.

    3. Safety and tolerability of treatment regimen as measured by the frequency of adverse events [From the start of treatment until 90 days after completion of treatment (up to 27 months).]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Washington University School of MedicineSaint LouisMissouriUnited States63110

    Sponsors and Collaborators

    • Washington University School of Medicine
    • Xcovery Holding Company, LLC

    Investigators

    • Principal Investigator: Daniel Morgensztern, MD, Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT04373369
    Other Study ID Numbers:
    • 202007036
    First Posted:
    May 4, 2020
    Last Update Posted:
    Dec 30, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Washington University School of Medicine
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 30, 2021