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

NCT06110572 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: VICCTHOP2206NCI-2023-08550
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Extensive Stage Lung Small Cell Carcinoma; Stage IV Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Rates of treatment-related adverse events

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

  Up to 30 days after completion of study treatment

• 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

  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 (6)

• Overall Survival

  Up to 3 years

• Overall Response Rate

  Up to 3 years

• Disease Control Rate

  Up o 3 years

• Intracranial Control Rate

  Up to 3 years

• Thoracic Control Rate

  Up to 3 years

Study Arms (1)

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

EXPERIMENTAL

Description INDUCTION PHASE: Patients receive carboplatin IV and atezolizumab IV on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive TBI BID on day 18 or 19 of cycle 1 and beginning 2-3 days later, H-RT daily over 7 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive atezolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the trial.

Drug: Carboplatin; Biological: Atezolizumab; Drug: Etoposide; Radiation: Total Body Irradiation; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging

Interventions

Carboplatin DRUG

Given by IV

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

Atezolizumab BIOLOGICAL

Given by IV

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

Etoposide DRUG

Given by IV

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

Total Body Irradiation RADIATION

Undergo Total Body Irradiation

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

Hypofractionated Radiation Therapy RADIATION

Undergo Hypofractionated Radiation Therapy

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

Magnetic Resonance Imaging PROCEDURE

Undergo Magnetic Resonance Imaging

Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)

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 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
• Platelet count ≥ 100 x 10\^9/L
• Lymphocyte count ≥ 0.5 x 10\^9/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN, alanine aminotransferase (ALT) ≤ 2.5 x ULN and alkaline phosphatase ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 50 mL/min if creatinine (Cr) \> 1.5 x ULN. GFR can also be utilized. If no local calculation guidance on CrCl, should be calculated according to Cockcroft-Gault Method
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulation therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
• Negative HIV test at screening, with the following exception: patients with positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200, and have an undetectable viral load
• Negative Hepatitis B surface antigen at screening
• Presence of brain metastases allowed (should undergo management with surgery and/or radiation therapy if symptomatic prior to TESSERACT radiation regimen; upfront cranial irradiation not mandatory on protocol if asymptomatic)
• Contraceptive use should be initiated or continued per guidance in labeling for approved chemotherapies

You may not qualify if:

• 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
• 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.
• History of prior malignancy within 3 years of enrollment, except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ (e.g. cervix or non- invasive bladder cancer) or other malignancy with minimal risk of metastasis or death (survival \> 90% at 5 years)
• Receipt of prior courses of cytotoxic chemotherapy or anti-neoplastic biologic/immunotherapy for current malignancy (other than the current course of therapy). Patients may have undergone 1 cycle of 1st line of systemic therapy for SCLC prior to enrollment as long as the systemic therapy is congruent with what is included in the protocol and part of the current course of therapy.
• Prior radiotherapy that would preclude delivery of protocol- based radiotherapy to normal organ tolerance per patient's study physician
• Receipt of live attenuated vaccine within 28 days of cycle 1, day 1 (C1D1), and for 5 months after the last dose of atezolizumab.
• Use of prohibited concomitant drug
• Concurrent enrollment in another clinical trial (unless observational or within follow-up period)
• Known, pathologically confirmed malignant pleural effusions (diagnostic evaluation of pleural effusions are recommended but not required for study entry, especially if sampling is deemed technically challenging at discretion of treating physician)
• Uncontrolled pleural or pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed
• History of leptomeningeal disease
• Uncontrolled tumor-related pain: Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy can undergo treatment with palliative radiotherapy prior to enrollment at discretion of treating physicians. Patients should be recovered from effects of radiation and there is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) can be considered for loco-regional therapy at discretion of treating physician prior to enrollment.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; atezolizumab; Etoposide; Whole-Body Irradiation; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

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; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Evan Osmundson, MD, PhD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 31, 2023
• Study Start: April 24, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)