Liver Directed RT + Chemo-immunotherapy for ES-SCLC

NCT04923776 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAT0174
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether radiation treatment directed at liver metastases can be safely added to standard of care treatment for extensive stage small cell lung cancer (ES-SCLC). The current standard treatment for people who have ES-SCLC is chemotherapy including drugs called carboplatin and etoposide, that is combined with a type of immunotherapy called atezolizumab. However, patients with liver involvement of their ES-SCLC don't respond as well to this treatment. The study aims to answer whether adding radiation directed at liver metastases can improve responses to standard chemo-immunotherapy in this patient population. All study participants will get the same study intervention, which will be chemo-immunotherapy and radiation therapy.

Conditions

Small-cell Lung Cancer

Keywords

Liver metastases; Radiation chemotherapy; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Rate

  Progression free survival rate at 6 months will be measured to assess the efficacy of liver-directed SBRT when added to standard of care atezolizumab + chemotherapy. 6-month PFS rate will be defined as the proportion of patients that are progression free and alive at 6 months from the start of treatment.

  Up to 6 months

Secondary Outcomes (2)

• Overall Survival Rate

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

Study Arms (1)

Experimental: Chemotherapy+SBRT

EXPERIMENTAL

Addition of SBRT, directed at liver metastases, to standard of care (SOC) treatment atezolizumab+chemotherapy in SCLC. All patients must undergo a mandatory biopsy of a liver lesion prior to chemotherapy initiation. Cycle 1 of chemoimmunotherapy will be administered as per standard of care, with radiation planning to be done subsequently in anticipation of liver-directed SBRT.

Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Carboplatin DRUG

The dosage for this drug is area under the curve (AUC) 5 mg/ml/min intravenous, Day 1, every 21 days for 4 cycles. This is standard of care.

Also known as: Paraplatin

Experimental: Chemotherapy+SBRT

Etoposide DRUG

The dosage for this drug is 100 mg/m2 Intravenous, Days 1-3, every 21 days for 4 cycles. This is standard of care.

Also known as: Vepesid

Experimental: Chemotherapy+SBRT

Atezolizumab DRUG

The dosage for this drug is 1200 mg Intravenous, Day 1, every 21 days until disease progression. This is standard of care.

Also known as: Tecentriq

Experimental: Chemotherapy+SBRT

Stereotactic Body Radiation Therapy (SBRT) RADIATION

This radiotherapy is given within +/-3 days of cycle 2, 10 Gy 3 doses on alternating days. This is not standard of care and considered interventional.

Experimental: Chemotherapy+SBRT

Eligibility Criteria

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

You may qualify if:

• Age≥ 18 years
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group (VALG) staging system)
• No prior treatment for ES-SCLC
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients with a history of treated, asymptomatic CNS metastases are eligible providing they meet the following criteria
• Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord)
• No ongoing requirement for corticosteroids as therapy for CNS disease
• No stereotactic brain radiation within 7 days
• No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• Patients with new asymptomatic Central Nervous System (CNS) metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to randomization, if all other criteria are met.
• At least one liver metastasis measuring 1 cm.
• Measurable disease, as defined by RECIST v1.1, in addition to the liver lesion(s) to which SBRT is planned.
• Patients must submit a pre-treatment tumor tissue sample from a liver metastasis. Tumor tissue must be obtained prior to the start of treatment.
• Adequate hematologic and end organ function, defined by the following laboratory results:
• Absolute neutrophil count (ANC) ≥1500 cells/μL without granulocyte colony-stimulating factor support

You may not qualify if:

• Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥1 week prior to randomization
• Leptomeningeal disease
• Prior radiation treatment of SCLC outside of the CNS
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (\>1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN)
• Patients who are receiving denosumab prior to randomization must be willing and eligible to discontinue its use and replace it with a bisphosphonate while in the study.
• Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS \>90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
• a. Prior radiation for non-SCLC malignancies \>5 years prior to randomization will be permitted, with the exception of those who underwent liver-directed treatments
• Child-Pugh class B cirrhosis or worse
• History of liver-directed ablative therapy for any indication, including radiation, chemoembolization, radiofrequency ablation, or other similar modalities
• Women who are pregnant, lactating, or intending to become pregnant during the study
• Pregnant women are excluded from this study because carboplatin and etoposide are category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

Sponsors & Collaborators

• Brian Henick, MD: lead

Study Sites (1)

Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Carboplatin; Etoposide; atezolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Brian Henick, MD
• Organization: Columbia University

bh2682@cumc.columbia.edu

212-342-5162

Study Officials

• Brian Henick, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Assistant Professor of Medicine

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 11, 2021
• Study Start: September 20, 2021
• Primary Completion: September 13, 2023
• Study Completion: December 23, 2023
• Last Updated: December 30, 2024
• Results First Posted: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)