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

NCT ID: NCT04364048

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-18
• Study Completion Date: 2024-02-05

Brief 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.

Conditions

Lung Cancer; Non-small Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction durvalumab, chemoradiation, consolidation durvalumab

Induction durvalumab at 1500 mg intravenously (IV) on Day 1 of a four week cycle for 1 cycle, followed by concurrent definitive chemoradiation, followed by consolidation durvalumab at 1500 mg IV Day 1 of every 4 week cycle for up to 12 cycles.

Group Type: EXPERIMENTAL

Induction Durvalumab

Intervention Type: DRUG

Induction durvalumab at 1500 mg intravenously (IV) will be given on Day 1 of a four week cycle for 1 cycle,

Chemotherapy

Intervention Type: DRUG

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

Intervention Type: 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.

Consolidation durvalumab

Intervention Type: DRUG

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

Interventions

Induction Durvalumab

Induction durvalumab at 1500 mg intravenously (IV) will be given on Day 1 of a four week cycle for 1 cycle,

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Consolidation durvalumab

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

Intervention Type: DRUG

Other Intervention Names

IMFINZI; cisplatin; carboplatin; etoposide; pemetrexed; taxane; IMFINZI

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Providence Cancer Center, Earle A. Chiles Research Institute

OTHER

Sponsor Role: collaborator

Rachel Sanborn

OTHER

Sponsor Role: lead

Responsible Party

Rachel Sanborn

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rachel Sanborn, MD

Role: PRINCIPAL_INVESTIGATOR

Providence Cancer Institute

Locations

Rush University Medical Center

Chicago, Illinois, United States

Cancer Center of Kansas

Wichita, Kansas, United States

HealthPartners Institute

Minneapolis, Minnesota, United States

Summit Medical Group, P. A.

Berkeley Heights, New Jersey, United States

Providence Portland Medical Center

Portland, Oregon, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

LUN18-357

Identifier Type: -

Identifier Source: org_study_id