ADMIRAL Trial: Adaptive Mediastinal Radiation With Chemo-Immunotherapy

NCT04372927 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1007190NCI-2020-0241710459
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies two questions in patients with stage III NSCLC: 1) does it improve cancer control to add the drug Durvalumab, a type of immunotherapy, earlier in the treatment course; and 2) by intensifying treatment with durvalumab, is it possible to avoid mediastinal radiation to decrease side effects, without decreasing cancer control?

Conditions

Locally Advanced Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 1 Year Progression-free Survival Rate (PFS)

  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.

  Study enrollment to disease progression or death, whichever occurs first, for up to 1 year

Secondary Outcomes (4)

• Frequency and Severity of Pneumonitis

  Through study completion (up to 4 months)

• Overall Survival (OS)

  From study registration to death due to any cause

• Response Rate

  Through study completion (up to 4 months)

• Frequency of Adverse Events

  Through study completion (up to 4 months)

Study Arms (1)

Treatment (chemotherapy, durvalumab, radiation therapy)

EXPERIMENTAL

Patients with squamous cell cancer receive standard of care chemotherapy consisting of cisplatin on days 1, 8, 29, and 36, and etoposide on days 1-5 and 29-33. Cycles repeat every 4 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with non-squamous cell cancer receive standard of care chemotherapy consisting of cisplatin and pemetrexed on days 1, 22, and 43. Cycles repeat every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. All patients receive durvalumab IV over 1 hour Q4W. Radiation to the primary tumor will be given over 8-15 fractions during weeks 1-3 of chemotherapy. For patients who have residual disease in the mediastinal lymph nodes at week 9, radiation will be given to the lymph nodes starting week 11. Durvalumab is given for 2 years after completion of radiation in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Biological: Durvalumab; Drug: Etoposide; Radiation: Hypofractionated Radiation Therapy; Drug: Pemetrexed

Interventions

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 (chemotherapy, durvalumab, 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, 1428935-60-7

Treatment (chemotherapy, durvalumab, 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 (chemotherapy, durvalumab, radiation therapy)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated Radiotherapy, hypofractionation

Treatment (chemotherapy, durvalumab, radiation therapy)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Treatment (chemotherapy, durvalumab, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented non-small cell lung cancer (NSCLC)
• Stage III NSCLC according to American Joint Committee on Cancer (AJCC) staging version (v)8
• At least one mediastinal site of disease that is discontiguous from all other visible sites of disease and can be excluded from primary tumor site radiation (i.e. at least 10 mm separation between tumors)
• A maximum of 20 patients with bulky mediastinal disease will be allowed on this trial, defined as at least one contiguous mediastinal mass with minimum diameter \> 2 cm, that is not contiguous with the primary tumor (and therefore would not be irradiated during radiation to the primary tumor)
• No surgery for lung cancer for at least 3 years
• No other malignancies for at least 3 years, excluding low grade or non-invasive malignancies such as skin cancers, prostate cancers, and ductal breast carcinoma in situ (DCIS)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Age \>= 18 years at time of study entry
• Life expectancy of \>= at least 3 months
• Body weight \> 30 kg
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 (or 1.0) x (\>= 1500 per mm\^3)
• Platelet count \>= 100,000 per mm\^3
• 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
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x upper limit of normal (ULN)

You may not qualify if:

• Prior anti-CTLA-4, PD-1 or PD-L1 antibodies including durvalumab
• Prior chemotherapy in the past 3 years from consent
• 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
• Prior thoracic radiation that would preclude curative-intent radiation dose as outlined in this study
• 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
• 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 adverse events (AEs) or compromise the ability of the patient to give written informed consent
• History of leptomeningeal carcinomatosis

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

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

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

We enrolled one participant, then trial closed due to poor accrual. Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Jing Zeng
• Organization: University of Washington School of Medicine

jzeng13@uw.edu

206-598-4115

Study Officials

• Jing Zeng

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 4, 2020
• Study Start: December 10, 2021
• Primary Completion: April 23, 2022
• Study Completion: April 23, 2022
• Last Updated: June 13, 2023
• Results First Posted: June 13, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)