Durvalumab Followed by Chemoradiation and Consolidation Durvalumab for Stage III Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Induction Durvalumab Followed by Chemoradiation and Consolidation Durvalumab (MEDI4736) for Stage III Non-small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04364048
• Other study ID #: LUN18-357
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 18, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Single arm study of induction durvalumab (1500 mg IV) for 1 cycle (every 4 weeks), administered prior to starting concurrent definitive chemoradiation, followed by consolidation durvalumab (1500 mg IV every 4 weeks) for up to 12 cycles. The study will include an initial safety run-in portion. Patients in the safety run-in will be monitored through completion of induction durvalumab, chemoradiation, and 2 cycles of consolidation durvalumab for assessment of safety prior to completion of enrollment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: December 31, 2024
• Est. primary completion date: June 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age = 18 years at the time of consent.
• ECOG Performance Status of 0 or 1.
• Histological or cytological confirmation of stage III non-small cell lung cancer per AJCC, 8th edition, eligible for curative-intent concurrent chemoradiation. NOTE: subjects are not candidates for surgical resection either due to medical inoperability or surgically unresectable disease.
• Measurable disease according to RECIST 1.1 criteria.
• Plan for treatment with concurrent chemoradiation with a dose of radiation ranging

from 54-66 Gy:

• Planned mean dose delivery to the lung <20 Gy
• V20 <35%
• No prior therapy for stage III NSCLC.
• Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 24 hours of C1D1. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• Females of childbearing potential must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.
• Men who are sexually active with WOCBP must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.
• Life expectancy of at least 12 weeks per investigator discretion.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

• Prior therapy for stage III NSCLC
• Mixed histology with small cell lung cancer will not be allowed.
• Sequential chemoradiation will not be permitted.
• Induction and consolidation chemotherapy (separate from concurrent chemoradiation) will not be allowed.
• Prior exposure to anti-PD-1 or anti-PD-L1 antibodies including durvalumab.
• Current or prior use of immunosuppressive medication within 14 days before the first

dose of durvalumab. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• History of pulmonary fibrosis, interstitial lung disease, or pneumonitis requiring steroids.
• Active or prior documented autoimmune disease within the last 2 years. Patients with vitiligo, stable hypothyroidism, Grave's disease, or psoriasis not requiring systemic treatment are not excluded.
• Body weight < 30 kg
• Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, COPD, allergic rhinitis).
• Active infection requiring systemic therapy.
• Uncontrolled current illness that in the opinion of the investigator renders the investigational treatment plan unsafe.
• 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.

• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
• Active other malignancy; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Treatment with any investigational drug within 30 days prior to registration.
• History of organ transplantation (including allogeneic stem cell transplantation).
• Other medical or psychiatric conditions that in the opinion of the site investigator would preclude safe participation in this protocol. Eligibility Criteria for Consolidation Durvalumab
• Patients must have recovered from toxicities associated with prior chemoradiation to CTCAE < Grade 2.
• Patients must not have progressed following chemoradiation therapy, as measured on imaging per RECIST 1.1.
• Confirmation of ECOG Performance Status of 0 or 1.
• Any grade pneumonitis from prior chemoradiation will not be permitted.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Non-small Cell Carcinoma

Intervention

Drug:
• Induction Durvalumab
Induction durvalumab at 1500 mg intravenously (IV) will be given on Day 1 of a four week cycle for 1 cycle,
• Chemotherapy
Concurrent chemoradiation will be with platinum-based chemotherapy (cisplatin or carboplatin, with etoposide, taxane, or pemetrexed) selected at the treating physician's discretion. The chemotherapy regimen used should be administered per institutional standards following the prescribing guidelines for each drug

Radiation:
• Radiation
Treatment will be delivered using IMRT or 3DCRT using typically 6-10MV photons per institutional standards. 4D simulation and appropriate IGRT are encouraged. Radiation therapy must begin within one week of the first day of chemotherapy (or vice versa). Therapy will be 1.8-2 Gy per day; 5 days per week, excluding holidays per institutional standard as this is a standard of care regimen for this patient population. 54-66 Gy will be delivered.

Drug:
• Consolidation durvalumab
Durvalumab at 1500 mg intravenously (IV) will be given on Day 1 of a four week cycle for 12 cycles

Locations

Country	Name	City	State
United States	Summit Medical Group, P. A.	Berkeley Heights	New Jersey
United States	Rush University Medical Center	Chicago	Illinois
United States	HealthPartners Institute	Minneapolis	Minnesota
United States	Providence Portland Medical Center	Portland	Oregon
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Rachel Sanborn	AstraZeneca, Providence Cancer Center, Earle A. Chiles Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	12-month progression-free survival will be measured using imaging after completion of chemoradiation, prior to C1 consolidation durvalumab (1-42 days after completion of chemoradiation). This will be compared with PACIFIC trial 12-month progression-free survival as historical control.	12 months
Primary	Assess the frequency and severity of adverse events	Toxicity will be measured by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.	12 months
Secondary	Objective Response Rate (ORR)	ORR will be measured using two timepoints, per RECIST 1.1. "ORR1" will be assessed using baseline imaging in comparison to imaging obtained after completion of induction durvalumab and chemoradiation. "ORR2" will be assessed using imaging after completion of induction durvalumab and chemoradiation in comparison to imaging obtained while receiving, and after completion of, consolidation durvalumab.	12 months