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

NCT04610684 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN LUN19-427
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 6

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

Outcome Measures

Primary Outcomes (1)

• Intracranial Progression Free Survival (iPFS)

  Intracranial PFS is defined as the time from Day 1 of treatment until the criteria for intracranial disease progression is met as defined by RANO-BM or death as a result of any cause, whichever comes first. Progression disease is defined as 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 progressions).

  From C1D1 until death or up to a maximum of 6 months

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  From C1D1 until death or up to a maximum of 6 months

• Extracranial Progression Free Survival (PFS)

  From C1D1 until death or up to a maximum of 6 months

• Overall Survival (OS)

  From C1D1 until death or up to a maximum of 9 months

• Toxicity of Atezolizumab Plus Carboplatin and Etoposide

  From C1D1 until death or up to a maximum of 9 months

Study Arms (1)

Study Treatment Arm

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab

Interventions

Carboplatin 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.

Also known as: paraplatin

Study Treatment Arm

Etoposide 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.

Also known as: VP-16

Study Treatment Arm

Atezolizumab 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.

Also known as: Imfinzi

Study Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years with ability and willingness to provide informed consent.
• ECOG Performance Status of 0-2.
• Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) per Veterans Administration Lung Study Group (VALG).
• At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1 that has not been previously irradiated.
• 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.
• 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.
• 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.
• A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
• 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

You may not qualify if:

• 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.
• Leptomeningeal disease. Discrete dural-based metastases will be allowed without evidence of leptomeningeal disease.
• Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranial radiation is allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone \< 10 mg daily (or equivalent).
• History of interstitial pneumonitis from any cause.
• Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study as assessed by site investigator.
• 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.
• 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.
• 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.
• Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), Testing not required at screening.
• Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, or other oral anticoagulant (coumadin, DOAC).
• 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.

Sponsors & Collaborators

• Jeffrey Clarke: lead
• Genentech, Inc.: collaborator
• Duke University: collaborator

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

St. Vincent Anderson Regional Hospital

Anderson, Indiana, 46016, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Summit Health

Berkeley Heights, New Jersey, 07922, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Brain Neoplasms

Interventions

Carboplatin; Etoposide; atezolizumab; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Clinical Data Analyst
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Jeffrey Clarke, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 30, 2020
• Study Start: January 5, 2021
• Primary Completion: July 15, 2022
• Study Completion: September 20, 2022
• Last Updated: March 13, 2024
• Results First Posted: March 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)