Gene Therapy Clinical Trials

Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC

The purpose of this study is to test whether or not number of circulating cancer cells detected in the blood can be decreased the by combining the standard treatment (durvalumab) with Tremelimumab and additional chemotherapy

Stanford is currently accepting patients for this trial.

Stanford Investigator(s):

Intervention(s):

  • drug: Durvalumab
  • drug: Carboplatin
  • drug: Pemetrexed
  • drug: Paclitaxel
  • drug: Cisplatin
  • device: AVENIO ctDNA Surveillance Kit
  • drug: Tremelimumab

Eligibility


Inclusion Criteria:

   1. Histologically- or cytologically-documented NSCLC presenting with locally-advanced,
   unresectable stage III disease (Version 8 of AJCC Staging Manual) or NSCLC with
   locoregional recurrence after previous definitive treatment.

   2. For stage III or recurrent disease, must have completed platinum-based chemotherapy
   and radiation therapy to all known tumor sites (60 Gy +/- 10%). Must not have known
   progression of disease.

   3. Must be receiving consolidation durvalumab following completion of radiation and
   chemotherapy, and less than 32 weeks has elapsed from their first dose of durvalumab.
   (Patients may sign consent for study before start of durvalumab, but confirm
   eligibility and enroll only after first dose of durvalumab is received).

   4. Able to potentially receive further consolidation chemotherapy plus durvalumab and
   tremelimumab, but not be currently intended to receive additional systemic
   consolidation chemotherapy apart from this durvalumab.

   5. Pre-treatment tumor tissue or tumor DNA sample is believed to be available for
   analysis

   6. Aged 18 years or older

   7. Weight > 30kg

   8. Life expectancy ≥ 12 weeks

   9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

10. Absolute neutrophil count > 1.0 x 109/L (1000/mm3)

11. Platelets > 75 x 109/L (100,000/mm3)

12. Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)

13. 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)

14. 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.

15. 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

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

Exclusion Criteria:

Involvement in the planning and/or conduct of the study

2. Previous enrollment or randomization in the present study

3. Received Investigational product as part of another clinical study

4. Mixed small cell and non small cell lung cancer histology

5. History of another primary malignancy and currently undergoing active treatment.

Exception: May participate if receiving adjuvant endocrine therapy for breast or prostate
cancer.

6. 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. Systemic steroid administration required to manage toxicities arising from
radiation therapy delivered as part of the chemoradiation therapy for locally advanced
NSCLC is allowed.

7. Any unresolved toxicity CTCAE > Grade 2 from the prior chemoradiation 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) only after
   consultation with the Protocol Director / Principal Investigator.

   8. Any prior Grade ≥ 3 immune related adverse event (irAE) while receiving any
   previous immunotherapy agent, or any unresolved irAE > Grade 1) that may limit subject
   from continuing durvalumab during the study

   9. Recent major surgery within 4 weeks prior to entry into the study (excluding the
   placement of vascular access) that would prevent administration of study drug.

   10. Active or prior documented autoimmune or inflammatory disorders which is likely to
   limit the subjects ability to continue 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]). Those with history of autoimmune or inflammatory
   disorders who are currently tolerating durvalumab may be eligible to participate with
   approval from the PI. The following are also 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. Celiac disease controlled by diet alone

      11. History of primary immunodeficiency

      12. History of organ transplant requiring therapeutic immunosuppression

      13. History of hypersensitivity to carboplatin, pemetrexed, paclitaxel, or
      nab-paclitaxel that is likely to prevent re-administration of these agents

      14. Active infection including but not limited to:

   - Grade 3 or higher clinically significant infection

   - Active 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

   - Active known Hepatitis C (HCV). EXCEPTION: Subjects positive for HCV antibody are
   eligible only if polymerase chain reaction is negative for HCV RNA

   - Active known tuberculosis infection (clinical evaluation that may include clinical
   history, physical examination and radiographic findings, or tuberculosis testing in
   line with local practice).

   - Active known HIV infection

   15. Receipt of live attenuated vaccine within 30 days prior to the first dose of
   concurrent chemotherapy and durvalumab. Note: Subjects, if enrolled, should not
   receive live vaccine through 30 days after the last dose of chemotherapy concurrent
   with durvalumab.

   16. 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

      - 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.

      17. Female subjects who are pregnant or breast feeding; or subjects of
      reproductive potential of any gender who are not employing or who do not agree to
      employ an effective method of birth control prior to trial enrollment.ollment.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Samantha Wong
650-498-8495
I'm interested