A Trial With Chemotherapy, Immunotherapy, and Radiotherapy for Patients With Newly Diagnosed Stage IV Small Cell Lung Cancer

NCT04951115 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-08022492
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

This study is for subjects with untreated Stage IV small cell lung cancer. Subjects will be given radiation therapy for five days, followed by standard of care chemo-immunotherapy (etoposide + carboplatin or cisplatin + durvalumab) for 4 cycles. Subjects may continue to receive durvalumab after 4 cycles have been completed until disease progression.

Conditions

Small-cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Toxicities Grade 3 or Above Related to Therapy

  Measured by the number of adverse of events that are deemed definitely or probably related to the treatments given while receiving study treatment

  Up to 29 months

• Efficacy of Multi-site, Non-ablative Radiation to Standard Systemic Therapy for Patients With Extensive-stage Small Cell Lung, as Measured by a Change in Disease Response

  Progression free survival at 12 months

  Up to 12 months

Secondary Outcomes (3)

• Objective Response Rate, Determined by Disease Response Rate Defined by the RECIST 1.1 Criteria

  Through study completion (an average of 2 years)

• Overall Survival, Defined as the Time From First Study Treatment to the Time of Death From Any Cause

  Up to 12 months

• Pattern of Disease Progression, Defined by the Progression in Radiated Lesions vs. Non-radiated Lesions and the Rates of New Lesions as Determined by RECIST 1.1

  From baseline through progression of disease (approximately 12 months)

Other Outcomes (3)

• Evaluation of the Tumor-immune Microenvironment in Those That Respond to Treatment vs Those That do Not Respond

  Through study completion (an average of 2 years)

• Evaluation of the Circulating Immune Cell in Those That Respond to Treatment vs Those That do Not Respond

  Through study completion (an average of 2 years)

• Evaluation of Inflammatory Protein Composition in Those That Respond to Treatment vs Those That do Not Respond

  Through study completion (an average of 2 years)

Study Arms (1)

Radiation + Chemo-Immunotherapy

EXPERIMENTAL

Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Drug: Durvalumab; Radiation: Stereotactic Body Radiotherapy

Interventions

Carboplatin DRUG

AUC = 5-6 mg/mL per min on Day 1 of each 21-day cycle, for 4 cycles

Radiation + Chemo-Immunotherapy

Cisplatin DRUG

75-80 mg/m2 on Day 1 of each 21-day cycle, for 4 cycles

Radiation + Chemo-Immunotherapy

Etoposide DRUG

80-100 mg/m2 on Day 1, Day 2, and Day 3 of each 21-day cycle, for 4 cycles

Radiation + Chemo-Immunotherapy

Durvalumab DRUG

1500 mg on Day 1 of each 21-day cycle, for 4 cycles. Following this, 1500 mg once every 4 weeks until disease progression

Radiation + Chemo-Immunotherapy

Stereotactic Body Radiotherapy RADIATION

6 Gy of radiotherapy targeting multiple sites of intrathoracic disease on Days 1-5 of cycle 1.

Radiation + Chemo-Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years old
• Written informed consent from subject or from Health Care Proxy prior to performing any protocol-related procedures, including screening evaluations.
• Pathological diagnosis of SCLC from biopsy (core biopsy or fine needle aspiration); mixed-histology (NSCLC and SCLC) allowed
• ES-SCLC (American Joint Committee on Cancer, 8th edition, stage IV \[T any, N any, M1a or M1b\], or T3-4 due to multiple lung nodules that are too extensive or tumor or nodal volume that is too large to be encompassed in a tolerable radiation plan)
• Brain metastases allowed, but must be asymptomatic without the need for systemic steroids at doses more than 10 mg/day of prednisone or its equivalent, or treated with Whole Brain Radiation Therapy (WBRT) or Stereotactic Radiosurgery (SRS)
• Body weight \> 30kg
• ECOG Performance Status (PS) 0-1 at enrollment. ECOG PS 2 allowed if PS decline considered by treating study investigator to be secondary to SCLC
• At least 1 lesion that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with CT, PET-CT, or MRI and that is suitable for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
• No prior exposure to IO therapy including, but not limited to, anti-CTLA-4, anti-PD-1, antiPD-L1, and anti-PD-L2 antibodies
• Life expectancy of at least 12 weeks from the start of therapy
• Adequate baseline organ functions as defined below
• Hemoglobin ≥8.0 g/dL.
• Absolute neutrophil count ≥1.5 × 103/uL (use of granulocyte colony-stimulating factor is not permitted at screening).
• Platelet count ≥75 × 103/uL.
• Serum bilirubin ≤1.5 × the ULN. This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.

You may not qualify if:

• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
• Participation in another clinical study with a therapeutic investigational product during the last 4 weeks.
• Contraindications to platinum-based chemotherapy
• Contraindications to radiation therapy
• Prior radiation therapy to same site as proposed SBRT site
• Cannot tolerate radiation treatment position or immobilization
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable, as is use of bisphosphonate or RANKL inhibitor therapy for prevention of skeletal-related events from bone metastases.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of the investigational product and of low potential risk for recurrence.
• Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ).
• History Limited-Stage SCLC treated with concurrent chemo-radiation
• History of allogenic organ transplantation.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (3)

New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

New York-Presbyterian Queens

Flushing, New York, 11355, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Carboplatin; Cisplatin; Etoposide; durvalumab; 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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; 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

Limitations and Caveats

This study was terminated early and participant enrollment was low, resulting in a small sample size (N=6). Having a small sample size may reduce statistical reliability and generalizability of results.

Results Point of Contact

• Title: Ashish Saxena
• Organization: Weill Cornell Medicine

ahs9018@med.cornell.edu

646-962-2066

Study Officials

• Ashish Saxena, MD

  Weill Medical College of Cornell 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

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: July 6, 2021
• Study Start: July 12, 2021
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2024
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)