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Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation

ConditionsExtensive Stage Lung Small Cell CarcinomaStage IV Lung Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVanderbilt-Ingram Cancer Center

About this trial

This phase I/II trial studies the side effects, safety, and effectiveness of low dose radiation to the entire body (total body irradiation \[TBI\]) and higher dose radiation to known areas of cancer (hypofractionated radiation therapy \[H-RT\]) combined with atezolizumab and chemotherapy (carboplatin \& etoposide) in treating patients with small cell lung cancer that has spread to disease sites outside of the lung (extensive stage). Extensive stage disease has historically been treated with chemotherapy alone with consideration of chest (thoracic) radiation therapy for those with response to chemotherapy, as well as consideration of preventative radiation therapy to the head (prophylactic cranial irradiation). Emerging evidence supports the synergistic interactions between immunotherapy and radiation therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Combining TBI and H-RT with atezolizumab and chemotherapy may improve response to treatment.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years at time of informed consent

Histologically documented or cytologically confirmed diagnosis of extensive stage small-celllung cancer with evaluable disease per RECIST v1.1 criteria. Patients may be considered extensive-stage based on M1 disease per AJCC 8th edition, OR may be clinically staged as extensive-stage disease based on anatomical extent that would preclude the use of standard radiotherapy fields as assessed by the treating radiation oncologist.

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

Disqualifiers

Major surgery (requiring general anesthesia or at discretion of study physician) within 4 weeks prior to study enrollment that would prevent treatment with TESSERACT regimen

Known clinically significant (per study physician) acute or chronic infections including HIV (per inclusion criteria above), hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis (testing not required for tuberculosis [TB]). Patients with HCV must be on stable dose of antiviral therapy on study entry. Current treatment with antivirals for HBV is not allowed on study

Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina

Uncontrolled hypertension (average systolic blood pressure greater than or equal to 140 or average diastolic blood pressure greater than or equal to 90 despite optimal medical therapy). Patients with hypertension (systolic blood pressure [SBP] ≥ 140 and/or diastolic blood pressure [DBP] ≥ 90) may enroll provided that an effective anti- hypertensive regimen is initiated.

Trial design

Design model

Single group

Treatments tested in this trial

  • Carboplatin

    Drug

    Given by IV

  • Atezolizumab

    Biological/Vaccine

    Given by IV

  • Etoposide

    Drug

    Given by IV

  • Total Body Irradiation

    Radiation

    Undergo Total Body Irradiation

  • Hypofractionated Radiation Therapy

    Radiation

    Undergo Hypofractionated Radiation Therapy

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo Magnetic Resonance Imaging

Treatment groups

18 Participants
are divided into 1 treatment group
Group A: Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Rates of treatment-related adverse events

Graded by Common Terminology Criteria in Adverse Events version 5.0 (Grade 2-5).

Time frame
Up to 30 days after completion of study treatment
2

Progression-free survival

Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Kaplan-Meier estimates and associated statistics and corresponding 95% confidence intervals will be presented by treatment group

Time frame
From consent to the date of the first documentation of objective progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first, assessed up to 6 months

Secondary outcomes

1

Overall Survival

Time frame
Up to 3 years
2

Overall Response Rate

Defined according to RECIST/Immune-Modified (i)RECIST criteria.

Time frame
Up to 3 years
3

Disease Control Rate

Defined as the percentage of patients who have achieved complete response (CR), partial response (PR) or stable disease (SD). Exact Binomial test and 95% confidence interval (CI) will be used to assess DCR.

Time frame
Up o 3 years
4

Intracranial Control Rate

Defined as the percentage of patients who have SD, PR, CR or no evidence of disease (NED) in the brain. Exact Binomial test and 95% CI will be used to assess intracranial control rate.

Time frame
Up to 3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Vanderbilt-Ingram Cancer Center

Lead sponsor

Genentech, Inc.

Collaborator

Source ClinicalTrials.gov
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