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

NCT04364048 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: LUN18-357
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (2)

• 12-Month 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) per RECIST 1.1. RECIST 1.1 Criteria for Response are: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

  From the time of treatment initiation until progression, up to 12 months

• Evaluate the Safety and Feasibility of Induction Durvalumab Using NCI CTCAE v5.0 for Toxicity Grading.

  All subjects receiving at least one dose of durvalumab will be evaluable for toxicity. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, will be used for toxicity grading. Please refer to the study calendar for the schedule of toxicity assessment.

  12 months

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  12 months

Study Arms (1)

Induction durvalumab, chemoradiation, consolidation durvalumab

EXPERIMENTAL

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; Drug: Chemotherapy; Radiation: Radiation; Drug: Consolidation durvalumab

Interventions

Induction Durvalumab DRUG

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

Also known as: IMFINZI

Induction durvalumab, chemoradiation, consolidation durvalumab

Chemotherapy 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

Also known as: cisplatin, carboplatin, etoposide, pemetrexed, taxane

Induction durvalumab, chemoradiation, consolidation durvalumab

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.

Induction durvalumab, chemoradiation, consolidation durvalumab

Consolidation durvalumab DRUG

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

Also known as: IMFINZI

Induction durvalumab, chemoradiation, consolidation durvalumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rachel Sanborn: lead
• AstraZeneca: collaborator
• Providence Cancer Center, Earle A. Chiles Research Institute: collaborator

Study Sites (5)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

HealthPartners Institute

Minneapolis, Minnesota, 55440, United States

Location

Summit Medical Group, P. A.

Berkeley Heights, New Jersey, 07922, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

durvalumab; Drug Therapy; Cisplatin; Carboplatin; Etoposide; Pemetrexed; taxane; Radiation

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Physical Phenomena

Results Point of Contact

• Title: Andrew Benson
• Organization: Hoosier Cancer Research Network

abenson@hoosiercancer.org

317-921-2050

Study Officials

• Rachel Sanborn, MD

  Providence Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 27, 2020
• Study Start: June 18, 2020
• Primary Completion: June 20, 2023
• Study Completion: February 5, 2024
• Last Updated: December 20, 2024
• Results First Posted: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)