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Adjuvant Durvalumab for Early Stage NSCLC Patients With ctDNA Minimal Residual Disease
Trial ID: NCT04585477
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.
Adjuvant Durvalumab for Early comStage NSCLC Patients With ctDNA Minimal Residual Disease
* Pathologically (histologically or cytologically proven) NSCLC. Tumors with any component
of small cell lung cancer are not allowed. Must NOT be known positive for EGFR TKI
sensitizing mutation (Exon 19 deletion or L858R mutation), or ALK/ ROS1 rearrangement.
Exception: EGFR mutant NSCLC with PD-L1 expression of 1% or higher is allowed if not
planned to receive adjuvant EGFR TKI).
- AJCC 8th edition clinical or pathological stage IA2 to IIIC disease. Stage IA1 tumors
are excluded unless recurrent with radiographic solid component -or- pathologic
invasive component of > 10 mm.
- Received therapy with surgery and/or definitive (curative intent) radiation. Note: May
have received chemotherapy.
- Completed all intended therapy (surgery, radiation, and/or chemotherapy) - AND- no
more than 32 weeks has elapsed after the last day of this therapy
- No known residual disease after intended therapy, for example:
- No positive margins after surgery without adjuvant radiotherapy
- No disease recurrence (in the investigator's assessment)
- Pre-treatment tumor tissue or tumor DNA sample is believed to be available for
- Not received immunotherapy (PD-1, PD-L1, or CTLA-4 antibodies) or be intended to
receive immunotherapy, apart from this study.
- Not received another systemic anti-cancer investigational product during the 4 weeks
prior to enrollment.
- Aged 18 years or older
- ECOG Performance Status of 0 or 1 (Appendix B)
- Life expectancy ≥ 12 weeks
- Acceptable laboratory parameters:
- Absolute neutrophil count > 1.0 x 109/L
- Platelets > 75 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- Creatinine ≤ 1.5 x ULN, OR creatinine clearance > 40 mL/min, by either 24 hour
urine collection or the Cockcroft Gault formula
- 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
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (ULN)
- Ability to understand and the willingness to sign the written IRB approved informed
- Women of childbearing potential or their male partner must agree to use a highly
effective method of contraception from enrollment until 8 months after final study
therapy. (see section 4.6.1)
- Involvement in the planning and/or conduct of the study
- Previous enrollment or randomization in the present study
- History of Grade 3 or higher pneumonitis from prior radiation; patients with grade 2
radiation pneumonitis may be considered for enrollment with permission from the
Protocol Director or Co-Director.
- History of another primary malignancy and currently undergoing active treatment
Exception: May participate if receiving adjuvant endocrine therapy for breast or
- Expected to require ongoing chronic treatment with immunosuppressive medication after
Exceptions: intranasal and inhaled corticosteroids or systemic corticosteroids at
physiological doses, not to exceed 10 mg/day of prednisone equivalent
- 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 > 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) with
permission from the Protocol Director / Co-Director.
- 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:
a. Vitiligo or alopecia b .Hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement c. Chronic skin condition not requiring systemic therapy d. Those
without active disease in the last 5 years may be included with permission from the
Protocol Director / Co-Director.
e. Celiac disease controlled by diet alone
- History of primary immunodeficiency
- History of organ transplant requiring therapeutic immunosuppression
- Active infection including but not limited to:
- Known Tuberculosis
- Known Hepatitis B [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.
- Known Hepatitis C (HCV) EXCEPTION: Subjects positive for HCV antibody are
eligible only if polymerase chain reaction is negative for HCV RNA
- Known HIV infection
- Receipt of live attenuated vaccine within 30 days prior to enrollment. 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.
- Uncontrolled intercurrent illness, including but not limited to clinically
- Ongoing or active Grade 3 or higher infection
- Symptomatic congestive heart failure
- Uncontrolled hypertension
- Unstable angina pectoris
- Cardiac arrhythmia
- Interstitial lung disease
- Serious chronic gastrointestinal conditions associated with diarrhea
- Psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the
ability of the subject to give written informed consent.
- Female subjects who are pregnant or breast feeding.
- Any other medical condition that, in the investigator's opinion, makes the subject
unsuitable for enrollment and study procedures.
device: AVENIO ctDNA Surveillance Kit