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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04364048
Recruitment Status : Recruiting
First Posted : April 27, 2020
Last Update Posted : July 8, 2020
Sponsor:
Collaborators:
AstraZeneca
Providence Cancer Center, Earle A. Chiles Research Institute
Information provided by (Responsible Party):
Rachel Sanborn, Hoosier Cancer Research Network

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

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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 : November 2021
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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




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.



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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 table below. All screening labs to be obtained within 14 days prior to registration.

    • Hemoglobin ≥ 9.0 g/dL
    • White blood cell (WBC) ≥ 3,000/mm3
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • Calculated creatinine clearance ≥ 40 mL/min
    • Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 x institutional ULN
    • Alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN
  • Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. 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 activity or to use 2 forms of effective methods of contraception from the time of informed consent until 180 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving study drug and who are sexually active with WOCBP will be instructed to adhere to contraception from the time of informed consent and for a period of 180 days after treatment discontinuation.
  • 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:

  • 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.
  • 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 monotherapy.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04364048


Contacts
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Contact: Rachel Sanborn, MD 503-215-2614 rachel.sanborn@providence.org
Contact: Robyn Lillie, RN 3176345842 ext 60 rlillie@hoosiercancer.org

Locations
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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
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Principal Investigator: Rachel Sanborn, MD Providence Cancer Institute
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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    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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