Adaptive SBRT Plus Chemoimmunotherapy for ES-SCLC

NCT05403723 | Suspended Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 2464GCCC_HP-00110765
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is trial studying the safety of adaptive stereotactic body radiotherapy (SBRT) combined with durvalumab immunotherapy, platinum chemotherapy, and etoposide chemotherapy in platinum refractory extensive stage small cell lung cancer (SCLC).

Conditions

Extensive-stage Small-cell Lung Cancer

Keywords

Lung Cancer; Chemoimmunotherapy; Stereotactic Body Radiotherapy; Durvalumab; Platinum; Etoposide

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events (AEs)

  Number of patients that experience Adverse Events (AEs) assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse Events will be described by Type, Category, including only most severe Grade experienced by a single patient.

  Up to 2.5 years

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  Up to 2.5 years

Study Arms (1)

Single Treatment Arm

EXPERIMENTAL

Eligible patients will complete 2 cycles of study treatment with durvalumab, platinum (cisplatin or carboplatin per investigator choice), and etoposide. Patients will then undergo standard of care restaging imaging. Those patients who have a partial or complete response will continue with combination systemic therapy, without additional intervention. In patients with less than a partial response (stable disease or progressive disease), SBRT will be given prior to cycle 3 of systemic therapy. The radiotherapy will be given in 5 fractions of 6 Gy to the primary tumor site. See study schema. Patients who undergo SBRT will resume systemic therapy within 2 weeks of completing SBRT and the interval between cycle 2 and cycle 3 should not exceed 6 weeks. Subsequent restaging imaging will continue as per standard of care. All patients will continue maintenance therapy with durvalumab until confirmed progressive disease.

Drug: Durvalumab 50 MG/1 ML Intravenous Solution; Drug: Etoposide Injection; Drug: Cisplatin; Drug: Carboplatin; Device: Stereotactic Body Radiotherapy

Interventions

Durvalumab 50 MG/1 ML Intravenous Solution DRUG

Durvalumab (1500 mg durvalumab via IV infusion) in combination with platinum doublet chemotherapy will be administered to patients once every 3 weeks for up to 4 cycles plus SBRT (platinum resistant group) or without SBRT (platinum sensitive group). Each 3-week of chemoimmunotherapy interval is considered a cycle. Patients with platinum sensitive disease will receive the combination of durvalumab and chemotherapy (total of four cycles) while those with platinum resistant SCLC will receive SBRT and continue to receive up to two additional cycles of treatment with durvalumab along with platinum/etoposide (not to exceed a total of four6 cycles of chemoimmunotherapy including 2 cycles obtained prior to SBRT). Following completion of 4-6 cycles of combination therapy, patients in both groups will continue with maintenance durvalumab (1500 mg) in q4w cycles until disease progression.

Single Treatment Arm

Etoposide Injection DRUG

A platinum/etoposide doublet will be administered according to institutional standards. Platinum-etoposide will consist of etoposide 80-100 mg/m2 on days 1-3 of each cycle along with a choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle).

Single Treatment Arm

Cisplatin DRUG

A platinum/etoposide doublet will be administered according to institutional standards. Platinum-etoposide will consist of etoposide 80-100 mg/m2 on days 1-3 of each cycle along with a choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle).

Also known as: Platinum

Single Treatment Arm

Carboplatin DRUG

A platinum/etoposide doublet will be administered according to institutional standards. Platinum-etoposide will consist of etoposide 80-100 mg/m2 on days 1-3 of each cycle along with a choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle).

Also known as: Platinum

Single Treatment Arm

Stereotactic Body Radiotherapy DEVICE

Patients will receive palliative radiation to the primary tumor site up to 30 Gy for 1 week given as 5 daily fractions of 6 Gy each or 27 Gy as 3 fractions of 9 Gy administered every other day.

Also known as: SBRT

Single Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥10.0 g/dL
• Absolute neutrophil count (ANC) ≥1.5 × 109 /L
• Platelet count ≥100 × 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Creatinine WNL or if \>ULN, then measured creatinine clearance (CL) \>50 mL/min or calculated creatinine CL\>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks prior to first dose of IP
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study PI/Sponsor
• Major surgical procedure within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of IP and of low potential risk for recurrence

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Interventions

durvalumab; Etoposide; Cisplatin; Platinum; Carboplatin; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Coordination Complexes; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Taofeek Owonikoko, MD, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2022
• First Posted: June 3, 2022
• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)