Lung Cancer Clinical Trial

Safety and Efficacy of Consolidative Hypofractionated Radiation Therapy (hfRT) for Boosting the Residual Primary Lung Cancer With Durvalumab

Summary

This study is designed to determine if combining consolidative radiation therapy (RT) using a hypofractionated regimen (hfRT) (2 fractions) for boosting the residual primary lung cancer with adjuvant anti-PD-L1 therapy concurrently is safe and will provide better tumor control locoregionally and distantly than either modality alone.

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Full Description

For safety reasons, consolidative hfRT will start from 6.5Gy x 2 fractions and dose escalate to 10Gy x 2 fractions in a 3+3 design. Consolidative hfRT will be delivered one to two months after finishing definitive chemoradiation therapy (dCRT) and concurrently with adjuvant anti-PD-L1 therapy using durvalumab in stage III non-small cell lung cancer (NSCLC).

At the final determined consolidative hfRT dose level, a total of thirty-two subjects with pathologically documented stage III NSCLC treated with dCRT will be enrolled for data analyses.

Follow-up assessments will occur every 3 months during durvalumab therapy for the first two years, then every 4-6 months after 2 years from study registration until confirmed disease progression or death. Primary endpoints include the safety of boost hfRT and concurrent anti-PD-L1 therapy adjuvantly following dCRT, and the 12-month progression-free survival to compare with historical results.

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Eligibility Criteria

Inclusion Criteria:

Pathologically diagnosed NSCLC (squamous cell carcinoma, adenocarcinoma, large- cell carcinoma, or non-small-cell lung cancer not otherwise specified), clinical stage III (AJCC 8th Ed.))
At time of consent, potential subjects must be a candidate for dCRT OR Must have received dCRT with at least 2 cycles of platinum-based chemotherapy concurrent with conventional fractionated radiation therapy with a total dose of 5700 - 6300 cGy
Patients must be aware of the nature of his/her disease and willingly provide written, informed consent. Including 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 (e.g., Health Insurance Portability and Accountability Act in the US) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Age > 19 years at time of study entry
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at time of enrollment.
Life expectancy of > 12 weeks

Adequate normal organ and marrow function as defined below:

Hemoglobin ≥9.0 g/dL (5.59 mmol/L) (patients can be transfused to meet this criterion)
Absolute neutrophil count (ANC) > 1500 per mm3
Platelet count ≥100 x 109/L (>100,000 per mm3)
Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal.
Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula
Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria:

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4
Participation in another clinical study with an investigational product during the last 4 weeks
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
Mixed small cell and non-small cell lung cancer histology
Patients who receive sequential chemoradiation therapy for locally advanced NSCLC
Patients with locally advanced NSCLC who have progressed during definitive platinum based, concurrent chemoradiation therapy
Any unresolved toxicity NCI CTCAE Grade >2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
Major surgical procedure (as defined by the investigator) within 28 days to the first dose of immunotherapy (excluding the placement of vascular access) that would prevent administration of study drug or radiation therapy.
History of allogenic organ transplantation.
Active or prior documented autoimmune or inflammatory disorders within the past 2 years (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]).
Known allergy or hypersensitivity to Durvalumab or any excipient.
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 ≥5 years before the informed consent 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 without evidence of disease
History of primary immunodeficiency
Known history or active infection of tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab therapy.
Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
Previous history of RT (other than RT as part of the dCRT for the current course of NSCLC) involving any part of lungs, chest wall, thoracic spine or breast(s).
Judgment by the investigator that the patient is unsuitable to participate in the study for any condition and the patient is unlikely to comply with study procedures, restrictions and requirements.
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 30 minutes at 5 minutes apart)

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

43

Study ID:

NCT04748419

Recruitment Status:

Recruiting

Sponsor:

Chi Zhang

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There is 1 Location for this study

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University of Nebraska Medical Center
Omaha Nebraska, 68198, United States More Info
Amberley Nurse Coordinator, RN
Contact
402-836-9171
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

43

Study ID:

NCT04748419

Recruitment Status:

Recruiting

Sponsor:


Chi Zhang

How clear is this clinincal trial information?

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