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Adjuvant Durvalumab for Early Stage NSCLC Patients With ctDNA Minimal Residual Disease

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ClinicalTrials.gov Identifier: NCT04585477
Recruitment Status : Not yet recruiting
First Posted : October 14, 2020
Last Update Posted : November 27, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Stanford University

Brief Summary:
In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Non-small Cell Lung Cancer Stage I Non-small Cell Lung Cancer Stage II Non-small Cell Lung Cancer Stage III Device: AVENIO ctDNA Surveillance Kit Drug: Durvalumab Phase 2

Detailed Description:

Primary Objective:

The primary objective of this study is to measure the change in ctDNA from trial enrollment to after 2 cycles of adjuvant durvalumab in subjects with stage I to III NSCLC who had positive ctDNA following definitive treatment with surgery or radiation and completion of adjuvant standard of care chemotherapy. Secondary Objectives

  1. To compare disease free survival (DFS)
  2. To compare overall survival (OS)
  3. To evaluate the frequency and severity of toxicity
  4. To evaluate the severity of toxicity

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Durvalumab for Early comStage NSCLC Patients With ctDNA Minimal Residual Disease
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Cohort 1 minimal residue disease positive(MRD+)

Subjects with detectable ctDNA (MRD+) will receive up to 12 cycles of durvalumab (1500mg dose by intravenous (by vein) injection every 28 days). ctDNA will be re checked following 2 cycles (8 weeks) of durvalumab and compared to baseline levels. In the absence of progression or toxicity after 2 cycles, subject will continue with durvalumab to complete 1 year of treatment about 10 additional cycles).

Subjects will be monitored for secondary endpoints of progression free survival (PFS) and overall survival (OS).

Device: AVENIO ctDNA Surveillance Kit
Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)
Other Name: The AVENIO ctDNA Surveillance Kit

Drug: Durvalumab
1500mg intravenous dose or 20mg/kg if weight is 30kg or less, manufactured by AstraZeneca
Other Names:
  • IMFINZI
  • MEDI4736

Active Comparator: Cohort 2 minimal residue disease negative (MRD-)
Subjects with undetectable ctDNA (MRD) will receive Standard of care and no treatment
Device: AVENIO ctDNA Surveillance Kit
Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)
Other Name: The AVENIO ctDNA Surveillance Kit




Primary Outcome Measures :
  1. Decrease in ctDNA Level [ Time Frame: 8 weeks ]
    Change in minimal residual disease (MRD) will be assessed on the basis of reduction of circulating tumor DNA (ctDNA) in the blood of participants in Cohort 1 MRD+ only. ctDNA is an indicator of MRD. The outcome will be reported as the number of participants who have a ≥ 3-fold drop in ctDNA levels after 2 cycles of durvalumab treatment, a number without dispersion.


Secondary Outcome Measures :
  1. Presence or absence of detectable ctDNA [ Time Frame: 8 weeks ]
    Circulating tumor DNA (ctDNA) in the blood is an indicator of minimal residual disease (MRD), a risk factor for future relapse or progression. The outcome will be reported as the number of Cohort 1 MRD+ participants for whom, following 2 cycles of durvalumab, ctDNA was detected, not detected, or unable to be determined, each a number without dispersion. Available data for Cohort 2 MRD- participants will also be reported for the 8-week timepoint.

  2. Overall survival (OS) [ Time Frame: 12 months ]
    Overall survival (OS) defined as the duration from study registration until death due to any cause. The outcome will be reported as the number of participants in each cohort known to be alive at 12 months after study registration, a number without dispersion.

  3. Disease-free survival (DFS) [ Time Frame: 8 weeks ]

    Disease-free survival (DFS) is defined as the number of participants remaining alive without disease progression (DP), symptomatic deterioration, or death due to any cause. DP is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as follows.

    • Complete Response (CR) = Disappearance of all target lesions
    • Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
    • Progressive disease (PD) = 20% increase in the sum of the diameters of target lesions (must be > 5 mm), unequivocal progression of non-target lesions, and/or the appearance of one or more new lesion(s)
    • Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome will be reported as the number of participants who meet the criteria for DFS, a number without dispersion.

  4. Related Adverse Events [ Time Frame: 12 months ]
    Related adverse events (AEs) are deleterious events determined to be possibly, probably, or definitely-related to durvalumab treatment. The outcome will be reported as the number of related AEs experienced by the participants in Cohort 1 MRD+ only (ie, durvalumab treatment cohort), a number without dispersion.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Histologically or cytologically documented NSCLC who present with stage I to III) disease (Version 8 of American Joint Committee on Cancer(AJCC) Staging Manual)
  2. Must have received primary treatment with surgery or definitive stereotactic body radiation therapy (SBRT), and not have known disease progression.
  3. Aged 18 years or older
  4. Life expectancy ³ 12 weeks
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B)
  6. Absolute neutrophil count > 1.0 x 109/L (1000/mm3)
  7. Platelets > 75 x 109/L (100,000/mm3)
  8. Hemoglobin ³ 9.0 g/dL (5.59 mmol/L)
  9. Measured creatinine clearance > 40 mL/min, by either 24 hour urine collection or the Cockcroft Gault formula

    Males:

    Mass(kg) x (140-Age) / 72 x serum creatinine (mg/dL)

    Females:

    Mass(kg) x (140-Age) x 0.85 / 72 x serum creatinine (mg/dL)

  10. Serum bilirubin £ 1.5 x upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician.
  11. Aspartate Aminotransferase (AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT) £ 2.5 x institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be £ 5 x ULN
  12. AVENIO ctDNA Surveillance Kit Circulating tumor DNA (ctDNA) test result demonstrating either minimal residual disease (MRD) positivity or negativity. Prospective subjects that have indeterminate or no results are NOT ELIGIBLE, but may re test (all other criteria must be met in window).
  13. Ability to understand and the willingness to sign the written IRB approved informed consent document.

Exclusion Criteria:

results are NOT ELIGIBLE, but may re test (all other criteria must be met in window).

13.Ability to understand and the willingness to sign the written IRB approved informed consent document.

Identify exclusion criteria.

  1. Involvement in the planning and/or conduct of the study
  2. Previous enrollment or randomization in the present study
  3. Participation in another clinical study with an investigational product (ie, non standard of care) during the last 4 weeks prior to the first dose of trial treatment
  4. Must not be planning to receive additional immunotherapy apart from this protocol
  5. Mixed small cell and non small cell lung cancer histology
  6. anaplastic lymphoma kinase (ALK) or ROS1 mutations, or has Epidermal Growth Factor Receptor (EGFR) mutations and PD L1 levels < 1%
  7. Known progression of disease following definitive surgery or radiation
  8. Developed Grade 2 or higher pneumonitis from prior radiation
  9. History of another primary malignancy and currently undergoing active treatment (ie, chemotherapy, hormonal therapy, biologics)
  10. Current or prior use of immunosuppressive medication within 14 days before enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  11. Any unresolved toxicity CTCAE > Grade 2 from prior therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

    • Subjects with Grade ³ 2 neuropathy will be evaluated on a case by case basis after consultation with the Protocol Director / Principal Investigator
    • Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab may be included (ie, hearing loss) only after consultation with the Protocol Director / Principal Investigator.
  12. Active or prior documented autoimmune or inflammatory disorders which could limit the subjects ability to receive durvalumab on the study (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc]). The following may be taken in to considerations as exceptions to this criterion:

    1. Vitiligo or alopecia
    2. Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
    3. Chronic skin condition not requiring systemic therapy
    4. Those without active disease in the last 5 years may be included, but only after consultation with the study physician
    5. Celiac disease controlled by diet alone
  13. History of primary immunodeficiency
  14. History of organ transplant requiring therapeutic immunosuppression
  15. Active infection including but not limited to:

    • Tuberculosis
    • Hepatitis B (HBV )[known positive results for HBV surface antigen (HBsAg) within 2 months prior to enrollment]. EXCEPTION: Subjects with a past or resolved HBV infection, defined as the presence of hepatitis B core antibody (anti HBc) and absence of HBsAg are eligible.
    • Hepatitis C (HCV). EXCEPTION: Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
  16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Subjects, if enrolled, should not receive live vaccine while receiving the investigational product (IP), and through 30 days after the last dose of IP.
  17. Uncontrolled intercurrent illness, including but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Uncontrolled hypertension
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Interstitial lung disease

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): NCT04585477


Contacts
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Contact: Grace Hwang (650) 723-0437 gracehw@stanford.edu

Locations
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United States, California
Stanford University
Stanford, California, United States, 94305
Contact: Grace Hwang    650-723-0437    gracehw@stanford.edu   
Principal Investigator: Joel W Neal, MD, PhD         
Sponsors and Collaborators
Stanford University
AstraZeneca
Investigators
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Principal Investigator: Joel W Neal, MD,PhD Stanford Universiy
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Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT04585477    
Other Study ID Numbers: IRB-54622
LUN0115 ( Other Identifier: OnCore )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: November 27, 2020
Last Verified: September 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: Yes
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm, Residual
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents