Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases

NCT ID: NCT04610684

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-05
• Study Completion Date: 2022-09-20

Brief Summary

This is a single arm, multicenter phase II trial for 60 patients with untreated extensive stage (ES) small cell lung cancer (SCLC) with asymptomatic brain metastases. Subjects will receive 4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). Each cycle equals 21 days. After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle. Subjects will receive treatment until disease progression, unacceptable drug-related toxicity, or withdrawal from study for any reason.

Conditions

Small-cell Lung Cancer; Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Treatment Arm

4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin 5-6 mg/mL/min AUC will be delivered over 30 - 60 minutes intravenously on Day 1 of each 21 day Cycle after completion of atezolizumab. For 4 cycles.

Etoposide

Intervention Type: DRUG

Etoposide 80-100 mg/m2 will be delivered over 60 minutes intravenously on Days 1-3 of each 21 day Cycle after completion of carboplatin (Day 1 only). For 4 cycles.

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 mg will be delivered over 60 (± 15) minutes intravenously on Day 1 of each 21 day Cycle for 4 cycles then continue as monotherapy maintenance with the same schedule.

Interventions

Carboplatin

Carboplatin 5-6 mg/mL/min AUC will be delivered over 30 - 60 minutes intravenously on Day 1 of each 21 day Cycle after completion of atezolizumab. For 4 cycles.

Intervention Type: DRUG

Etoposide

Etoposide 80-100 mg/m2 will be delivered over 60 minutes intravenously on Days 1-3 of each 21 day Cycle after completion of carboplatin (Day 1 only). For 4 cycles.

Intervention Type: DRUG

Atezolizumab

Atezolizumab 1200 mg will be delivered over 60 (± 15) minutes intravenously on Day 1 of each 21 day Cycle for 4 cycles then continue as monotherapy maintenance with the same schedule.

Intervention Type: DRUG

Other Intervention Names

paraplatin; VP-16; Imfinzi

Eligibility Criteria

Inclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

2. Age ≥ 18 years with ability and willingness to provide informed consent.

3. ECOG Performance Status of 0-2.

4. Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) per Veterans Administration Lung Study Group (VALG).

5. At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1 that has not been previously irradiated.

6. No prior treatment for metastatic disease. EXCEPTION: A single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment.

7. Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC.

8. Any prior cancer treatment must be completed at least 6 months prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline. NOTE: a single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment. NOTE: Extracranial radiation is allowed.

9. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.

10. Demonstrate adequate organ function as defined in the table below

• Absolute Neutrophil Count (ANC) ≥ 1.5K/mm3 without GCSF
• Hemoglobin (Hgb) ≥ 9 g/dL (without transfusion)
• Lymphocyte Count: ≥ 500/µL
• Platelet Count: ≥ 100,000/µL without transfusion
• Calculated creatinine clearance ≥ 50 cc/min OR Serum Cr < 1.5 x institutional ULN
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis
• Alanine aminotransferase (ALT) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis

11. Females of childbearing potential must have a negative serum pregnancy test within 3 days (72 hours) prior to enrollment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.

12. Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception, including at least one method with a failure of < 1% per year, from the time of informed consent until 150 days (5 months) after treatment discontinuation.

13. Negative hepatitis B surface antigen (HBsAg) test, negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Testing required at screening only if results are not known.

14. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. A positive HCV RNA test is sufficient to diagnose active HCV infection in the absence of an HCV antibody test.

15. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures.

Exclusion Criteria

1. Known active CNS metastases which are symptomatic. CNS metastases are considered asymptomatic if the patient does not require high dose or escalating corticosteroids or anticonvulsant therapy. Steroid dose must be equivalent to 2 mg of dexamethasone or less daily.

• Prior steroid use as part of an anti-emetic regimen with chemotherapy is allowed.
• Patients must be on a stable dose of corticosteroid. No tapering or decreasing dose within 7 days of enrollment.

2. Leptomeningeal disease. Discrete dural-based metastases will be allowed without evidence of leptomeningeal disease.

3. Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranial radiation is allowed.

4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)

5. Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone < 10 mg daily (or equivalent).

6. History of interstitial pneumonitis from any cause.

7. Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study as assessed by site investigator.

8. Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on Cycle 1 Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible. NOTE: Subjects with active tuberculosis are NOT eligible.

9. Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead.

10. History of myocardial infarction, NYHA class II or greater congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.

11. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), Testing not required at screening.

12. Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, or other oral anticoagulant (coumadin, DOAC).

13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). NOTE: Patients with indwelling catheters (e.g., PleurX®) are allowed.

14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.

15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.

16. History of allergic reactions to carboplatin or etoposide.

17. Intolerance of atezolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.

18. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, 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 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 of 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
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors

19. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.

20. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

21. Treatment with any investigational drug within 28 days prior to Cycle 1 Day 1.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

Jeffrey Clarke

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Clarke

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jeffrey Clarke, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

City of Hope

Duarte, California, United States

University of Illinois Cancer Center

Chicago, Illinois, United States

St. Vincent Anderson Regional Hospital

Anderson, Indiana, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Summit Health

Berkeley Heights, New Jersey, United States

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCRN LUN19-427

Identifier Type: -

Identifier Source: org_study_id