Hypofractionated Radiation Therapy After Durvalumab and Chemotherapy for the Treatment of Stage IV Extensive Stage Small Cell Lung Cancer, CASPIAN-RT Trial

NCT05161533 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: RG1121732NCI-2021-1242910810
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well hypofractionated radiation therapy after durvalumab and chemotherapy works to shrink tumors in patients with stage IV extensive stage small cell lung cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects than a conventionally fractionated radiation course. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin, cisplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding radiation after chemo and immunotherapy may help improve cancer control.

Conditions

Extensive Stage Lung Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The distribution of time to event outcomes will be evaluated using the method of Kaplan-Meier. Confidence intervals for median times will be determined using the Brookmeyer-Crowley method. Confidence intervals around landmark times will be determined using Greenwood's formula for the variance and based on a log-log transformation applied on the survival function. Binary proportions will be calculated with associated confidence intervals for binary outcomes, such as response. Means and/or medians will be calculated for continuous outcomes. Confidence bounds will be provided for means and quartiles and ranges for median values. All confidence bounds will be presented as 95% bounds.

  Up to 3 years

Secondary Outcomes (5)

• Incidence of grade 2 or higher pneumonitis

  Up to 90 days after the last dose of durvalumab

• Overall survival

  Up to 3 years

• Response rate

  Up to 3 years

• Healthcare related quality of life: EORTC QLQ-C30

  Up to 3 years

• Healthcare related quality of life: EORTC QLQ-LC13

  Up to 3 years

Study Arms (1)

Treatment (durvalumab, chemotherapy, radiation therapy)

EXPERIMENTAL

INDUCTION: Patients receive standard of care chemotherapy consisting of carboplatin or cisplatin and etoposide. Patients also receive durvalumab IV on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive durvalumab IV on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Beginning cycle 5 or 6 of durvalumab, patients undergo hypofractionated radiation therapy.

Drug: Carboplatin; Drug: Cisplatin; Biological: Durvalumab; Drug: Etoposide; Radiation: Hypofractionated Radiation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (durvalumab, chemotherapy, radiation therapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (durvalumab, chemotherapy, radiation therapy)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (durvalumab, chemotherapy, radiation therapy)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (durvalumab, chemotherapy, radiation therapy)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated

Treatment (durvalumab, chemotherapy, radiation therapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (durvalumab, chemotherapy, radiation therapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (durvalumab, chemotherapy, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Male or female \>= 18 years at the time of screening
• Able to provide written informed which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Histologically or cytologically documented extensive stage-small cell lung cancer (ES-SCLC) (American Joint Committee on Cancer \[AJCC\] 8th edition stage IV or tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan). Staging scans must include brain imaging with a computed tomography (CT) w/ contrast or magnetic resonance imaging (MRI) head and body imaging with a CT chest/abdomen/pelvis or a positron emission tomography (PET)/CT
• Patients with brain metastases are eligible provided they are asymptomatic, or treated and stable off steroids and anticonvulsants for at least 1 month before study entry
• Patients must be considered suitable to receive a platinum-based chemotherapy regimen as first-line treatment for ES-SCLC. Chemotherapy must contain either carboplatin or cisplatin in combination with etoposide
• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1 at enrollment
• Life expectancy \>= 12 weeks at enrollment
• Body weight \> 30 kg
• No prior exposure to immune-mediated therapy including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed cell death-1, anti-programmed cell death ligand-1, and anti-programmed cell death ligand-2 antibodies, excluding therapeutic anticancer vaccines, NOT INCLUDING if patients are currently within the first 4 cycles of chemotherapy and durvalumab for THIS diagnosis of ES-SCLC within the past 4 months
• Hemoglobin \>= 9.0 g/dL (within 3 prior months)
• Absolute neutrophil count \>= 1.5 x 10\^9/L (within 3 prior months)
• Platelet count \>= 75 x 10\^9/L (within 3 prior months)
• Serum bilirubin =\< 1.5 x the upper limit of normal (ULN) (within 3 prior months). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician
• In patients without hepatic metastasis: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN; for patients with hepatic metastases, ALT and AST =\< 5 x ULN (within 3 prior months)
• Measured or calculated creatinine clearance: of \> 40 mL/min as determined by Cockcroft-Gault (using actual body weight) (within 3 prior months)

You may not qualify if:

• Medical contraindication to platinum-etoposide
• Any anti-cancer therapies including chemotherapy, hormone therapy, or other immunotherapies in the 4 months prior to this diagnosis of ES-SCLC
• 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
• Any history of radiotherapy to the chest
• History of allogenic organ transplantation
• Has a peripheral nervous system (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis, etc.). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, 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, interstitial lung disease, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events 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 \>= 5 years before the first dose of the investigational product and of low potential risk for recurrence

Sponsors & Collaborators

• University of Washington: lead
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; durvalumab; Immunoglobulin G; Disulfides; Etoposide; Radiation Dose Hypofractionation; Radiation

Condition Hierarchy (Ancestors)

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; Metals, Heavy; Elements; Transition Elements; Metals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Physical Phenomena

Study Officials

• Jing Zeng

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

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: December 1, 2021
• First Posted: December 17, 2021
• Study Start: October 19, 2023
• Primary Completion: October 1, 2024
• Study Completion: December 31, 2024
• Last Updated: October 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)