Proton Based Cardiac Sparing Accelerated Fractionated RadioTherapy in Unresectable NSCLC

NCT03818776 | Terminated Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: CASE1518
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to treat participants with the combination of durvalumab (the study drug) and proton beam therapy. Proton beam therapy is a type of radiotherapy (RT) with a unique characteristic where the proton stops at a specific depth according to its energy. This may be advantageous in treating lung cancer because it allows for a sufficient tumor dose that may improve local control and survival while sparing normal organs at risk, such as the heart, lung, and spinal cord.

Conditions

Non-Small Cell Lung Cancer

Keywords

Durvalumab; PARTICLE-D

Outcome Measures

Primary Outcomes (1)

• Safety of intervention as defined by number of participants with Dose Limiting Toxicities (DLT) between first dose of Durvalumab and 30 days following completion of radiotherapy.

  Safety of intervention as defined by number of participants with DLT's between first dose of Durvalumab and 30 days following completion of radiotherapy. This is defined as 0 of 3 or 1 of 6 participants having no DLT of either Durvalumab or RT. DLT for RT defined as: 1. Grade 4-5 non-hematologic serious adverse events (SAEs) considered by the Investigators to be probably or definitely related to protocol treatment. 2. Grade 3 or higher cardiac adverse events (e.g. severely symptomatic congestive heart failure (CHF), myocarditis, pericardial effusion, myocardial infarction, symptomatic arrhythmia) considered by the Investigators to be probably or definitely related to protocol treatment. 3. Grade 3 or higher pulmonary adverse events (e.g. dyspnea/pneumonitis) considered by the Investigators to be probably or definitely related to protocol treatment and not responsive to steroids. 4. Failure to receive at least 54

  Up to 30 days following end of treatment

Secondary Outcomes (2)

• Feasibility of intervention defined by number of participants receiving full course of RT treatment and minimum of two doses of Durvalumab

  Up to 30 days following end of treatment

• Number of participants with Adverse Events according to CTCAE v5.0

  Up to 30 days following end of treatment

Study Arms (2)

Arm 1 - 60 CGyE in 20 fractions

EXPERIMENTAL

Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT. Radiation will follow dose escalation scheme: 60 CGyE in 20 fractions (3+3 participants, 3-6 total)

Drug: Durvalumab; Radiation: Proton beam therapy RT

Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a

EXPERIMENTAL

Proton based external beam radiation therapy with concurrent Durvalumab starting one week before RT. Radiation will follow dose escalation scheme: 69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)

Drug: Durvalumab; Radiation: Proton beam therapy RT

Interventions

Durvalumab DRUG

Durvalumab (MEDI4736) is an anti-PD-L1 monoclonal antibody immunotherapy for lung cancer. Participants will receive 1500mg durvalumab via intravenous (IV) infusion Q4W for up to a maximum of 12 months (up to 13 doses/cycles) with the last administration on week 48 unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. (N.b. If a participant's weight falls to 30kg (≤30 kg)), then the participant should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W after consultation between Investigator and Study Physician, until the weight improves to above 30 kg \>30 kg, at which point the participant should start receiving the fixed dosing of durvalumab 1500 mg Q4W).

Also known as: MEDI4736

Arm 1 - 60 CGyE in 20 fractions; Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a

Proton beam therapy RT RADIATION

Proton beam therapy is a type of RT where the proton stops at a specific depth according to its energy which allows for a sufficient tumor dose that may improve local control and survival while sparing normal organs at risk, such as the heart, lung, and spinal cord.

Arm 1 - 60 CGyE in 20 fractions; Arm 2 - 69 CGyE in 23 fractions followed by expansion cohort a

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status 0-2
• Body Weight \>30kg
• Must have anticipated life expectancy of at least 12 weeks
• Must be histologically or cytologically confirmed to be non-small cell lung cancer (NSCLC) confirmed by biopsy within 90 days of registration.
• Any tumor PD-L1 expression is allowed (including 0% to 100%, or unknown at time of study enrollment)
• AJCC 8th Stage IIA-IIIC.
• Must be deemed by Specialist or tumor board decision to not be a candidate for surgical resection or the participant refuses resection. Being deemed unresectable can be for any reason, including but not limited to: tumor location, tumor characteristics, operative risks, poor participant lung function, participant age or medical comorbidity.
• Must be deemed by Medical Oncologist or tumor board decision to not be a candidate for or able to tolerate standard cisplatinum based doublet concurrent chemoradiation therapy or the participant refuses chemotherapy. Being deemed not a chemotherapy candidate can be for any reason, including but not limited to: age, medical comorbidity, end organ dysfunction.
• Pulmonary function testing performed within 365 days prior to registration. . Sufficient lung function as judged by the primary investigator based on anticipated radiation fields, with a minimum of FEV1 ≥ 0.7 Liter or ≥ 30% and DLCO ≥ 30% with or without bronchodilator within 365 days prior to registration.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 (or 1.0) x (\> 1500 per mm3)
• Platelet count ≥75 x 109/L (\>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to participants 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

You may not qualify if:

• Prior large field thoracic radiation therapy is not allowed except for at the discretion of the primary investigator. Prior SBRT to contralateral lung, or breast radiation greater than 3 years prior is allowed. Other prior thoracic radiation is allowed at the discretion of the primary investigator.
• Prior radiation therapy, or immunotherapy for current diagnosis of NSCLC
• 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
• Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
• 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
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ (i.e. breast) without evidence of disease
• Low risk prostate cancer which has been treated or is undergoing active surveillance.
• Participants with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• Judgment by the investigator that the participant is unsuitable to participate in the study and the participant is unlikely to comply with study procedures, restrictions and requirements
• History of primary immunodeficiency
• 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:

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Proton Therapy

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)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Officials

• Debora Bruno, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Arm 1: 60 CGyE in 20 fractions (3+3 participants, 3-6 total) Arm 2: 69 CGyE in 23 fractions (3+3 participants, 3-6 total) Followed by expansion cohort at identified RP2 dose (12 participants)

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 28, 2019
• Study Start: August 30, 2019
• Primary Completion: January 27, 2022
• Study Completion: January 27, 2022
• Last Updated: February 15, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Will be shared with researchers who provide a methodologically sound proposal, to achieve aims in the approved proposal. To gain access, data requesters will need to sign a data access agreement

Locations

US (1)