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

• ClinicalTrials.gov Identifier: NCT04364048
• Recruitment Status: Recruiting
• First Posted: April 27, 2020
• Last Update Posted: January 21, 2022
• Sponsor: Rachel Sanborn
• Collaborators: AstraZeneca; Providence Cancer Center, Earle A. Chiles Research Institute
• Information provided by (Responsible Party): Rachel Sanborn, Hoosier Cancer Research Network

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Non-small Cell Carcinoma	Drug: Induction Durvalumab; Drug: Chemotherapy; Radiation: Radiation; Drug: Consolidation durvalumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Induction Durvalumab Followed by Chemoradiation and Consolidation Durvalumab (MEDI4736) for Stage III Non-small Cell Lung Cancer
• Actual Study Start Date: June 18, 2020
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: Induction Durvalumab; Induction durvalumab at 1500 mg intravenously (IV) will be given on Day 1 of a four week cycle for 1 cycle,; Other Name: IMFINZI; 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; Other Names: cisplatin; carboplatin; etoposide; pemetrexed; taxane; 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; Other Name: IMFINZI

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 12 months ]
   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.
2. Assess the frequency and severity of adverse events [ Time Frame: 12 months ]
   Toxicity will be measured by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 12 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Rachel Sanborn, MD; 503-215-2614; rachel.sanborn@providence.org

Contact: Robyn Lillie, RN; 3176345842 ext 60; rlillie@hoosiercancer.org

Locations

United States, Illinois

Rush University Medical Center; Recruiting

Chicago, Illinois, United States, 60612

Contact: Rina Seo 224-678-1196 rina_seo@rush.edu

Principal Investigator: Mary Jo Fidler, MD

United States, Kansas

Cancer Center of Kansas; Recruiting

Wichita, Kansas, United States, 67214

Contact: Shaughnessy Zimmerman 316-613-4314 shaughnessy.zimmerman@cancercenterofkansas.com

Principal Investigator: Shaker Dakhil, MD

United States, Minnesota

HealthPartners Institute; Recruiting

Minneapolis, Minnesota, United States, 55440

Contact: Kris Vukelich 952-993-6683 Kristen.Vukelich@ParkNicollet.com

Principal Investigator: Arkadiusz Dudek, MD

United States, New Jersey

Summit Medical Group, P. A.; Recruiting

Berkeley Heights, New Jersey, United States, 07922

Contact: Lorena Farrekk 973-436-1752 lfarrell@summithealth.com

Principal Investigator: Sarada Gurubhagavatula, MD

United States, Oregon

Providence Portland Medical Center; Recruiting

Portland, Oregon, United States, 97213

Sponsors and Collaborators

Rachel Sanborn

AstraZeneca

Providence Cancer Center, Earle A. Chiles Research Institute

Investigators

• Principal Investigator: Rachel Sanborn, MD; Providence Cancer Institute

More Information

• Responsible Party: Rachel Sanborn, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT04364048
• Other Study ID Numbers: LUN18-357
• First Posted: April 27, 2020
• Last Update Posted: January 21, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Cisplatin; Carboplatin; Etoposide; Pemetrexed; Durvalumab; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Antineoplastic Agents, Immunological; Immunologic Factors; Physiological Effects of Drugs