Clinical Trials /

QUILT-3.057: NANT Neoadjuvant Triple- Negative Breast Cancer (TNBC) Vaccine

NCT03554109

Description:

This is a randomized open-label phase 2 study to evaluate the efficacy and safety (as assessed by pCR) of the NANT Neoadjuvant TNBC Vaccine regimen (experimental arm) compared to the SoC dose-dense regimen of doxorubicin/cyclophosphamide followed by paclitaxel (control arm).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.057: NANT Neoadjuvant Triple- Negative Breast Cancer (TNBC) Vaccine
  • Official Title: An Open-Label Randomized Phase 2 Trial Of The NANT NEOADJUVANT Triple-Negative Breast Cancer (TNBC) VACCINE VS Standard-Of-Care For The Neoadjuvant Treatment Of Subjects With TNBC

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.057
  • NCT ID: NCT03554109

Conditions

  • Triple Negative Breast Cancer (TNBC)

Interventions

DrugSynonymsArms
LeucovorinGroup A
5-FluorouracilGroup A
Aldoxorubicin HClGroup A
nab-PaclitaxelGroup A
ETBX-011Group A
ETBX-051Group A
ETBX-061Group A
GI-4000Group A
GI-6207Group A
GI-6301Group A
AvelumabGroup A
ALT-803Group A
haNKGroup A
CyclophosphamideGroup A
Doxorubicin HCLGroup B
paclitaxelGroup B

Purpose

This is a randomized open-label phase 2 study to evaluate the efficacy and safety (as assessed by pCR) of the NANT Neoadjuvant TNBC Vaccine regimen (experimental arm) compared to the SoC dose-dense regimen of doxorubicin/cyclophosphamide followed by paclitaxel (control arm).

Detailed Description

      Treatment will be administered in 2 phases, a neoadjuvant phase and a postoperative phase.
      The neoadjuvant phase will be 18 weeks for patients enrolled in the experimental arm and 16
      weeks for those enrolled in the control arm.

      Following the neoadjuvant phase, all subjects will undergo determination of their current
      response status and appropriate breast surgery and node dissection after which assessment for
      pCR will be conducted following completion of neoadjuvant systemic therapy. Pathologists
      interpreting surgical specimens for pCR assessment will be blinded to the treatment arm.

      All subjects, regardless of whether or not they have achieved a pCR, will then enter the
      postoperative phase where they will receive adjuvant treatment. A small portion of the
      corresponding neoadjuvant therapy, either nab-paclitaxel or paclitaxel, will be administered
      as adjuvant treatment postoperatively. Adjuvant treatment will continue in the postoperative
      phase until the subject experiences unacceptable toxicity (not correctable with dose
      reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's
      best interest to continue treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Group AExperimentalNANT Neoadjuvant Triple Negative Breast Cancer Vaccine A combination of agents will be administered to subjects in this study: cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, avelumab, aldoxorubicin HCl, ALT-803, haNK, GI-4000, GI-6207, GI-6301, ETBX-011, ETBX-051 and ETBX-061
  • Leucovorin
  • 5-Fluorouracil
  • Aldoxorubicin HCl
  • nab-Paclitaxel
  • Avelumab
  • Cyclophosphamide
Group BActive ComparatorStandard treatment with a combination of doxorubicin, cyclophosphamide and paclitaxel.
  • Cyclophosphamide
  • Doxorubicin HCL
  • paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years.

          2. Able to understand and provide a signed informed consent that fulfills the relevant
             IRB or Independent Ethics Committee (IEC) guidelines.

          3. Histologically confirmed stage II or III TNBC. Subjects must be treatment naïve. TNBC
             is defined as breast cancer that lacks estrogen receptor (ER) and progesterone
             receptor (PgR) expression, and human epidermal growth factor receptor 2 (HER2)
             overexpression and/or amplification.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          5. Have at least 1 measurable lesion of ≥ 1.0 cm.

          6. Must have a recent FFPE tumor biopsy specimen and be willing to release the specimen
             for prospective and exploratory tumor molecular profiling. If an historic specimen is
             not available, the subject must be willing to undergo a biopsy during the screening
             period, if considered safe by the Investigator.

          7. Must be willing to provide blood samples prior to the start of treatment on this study
             for prospective tumor molecular profiling and exploratory analyses.

          8. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol.

          9. Agreement to practice effective contraception for female subjects of child-bearing
             potential and non-sterile males. Female subjects of child-bearing potential must agree
             to use effective contraception for up to 1 year after completion of therapy, and
             non-sterile male subjects must agree to use a condom for up to 4 months after
             treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
             tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
             spermicide, intrauterine devices (IUDs), and abstinence.

        Exclusion Criteria:

          1. Serious uncontrolled concomitant disease that would contraindicate the use of the
             investigational drug used in this study or that would put the subject at high risk for
             treatment-related complications.

          2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
             disease, and autoimmune disease associated with lymphoma).

          3. History of organ transplant requiring immunosuppression.

          4. History of or active inflammatory bowel disease (eg, Crohn's disease and ulcerative
             colitis).

          5. Inadequate organ function, evidenced by the following laboratory results:

               1. Absolute neutrophil count (ANC) < 1,000 cells/mm^3.

               2. Platelet count < 75,000 cells/mm^3.

               3. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).

               4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject
                  has documented Gilbert's syndrome).

               5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
                  > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).

               6. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
                  metastases, or >10 × ULN in subjects with bone metastases).

               7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.

               8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.

          6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
             clinically significant (ie, active) cardiovascular disease, cerebrovascular
             accident/stroke, or myocardial infarction within 6 months prior to first study
             medication; unstable angina; congestive heart failure of New York Heart Association
             grade 2 or higher; or serious cardiac arrhythmia requiring medication.

          7. Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute LVEF 10%
             below the institution's lower limit of predicted normal.

          8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
             continuous oxygen therapy.

          9. Positive results of screening test for human immunodeficiency virus (HIV).

         10. Current chronic daily treatment (continuous for > 3 months) with systemic
             corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
             excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
             reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

         11. Known hypersensitivity to any component of the study medication(s).

         12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
             reaction with any of the study medications.

         13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including
             ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone,
             nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit
             products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin,
             rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study
             day 1.

         14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8
             inducer (rifampin) within 14 days before study day 1.

         15. Participation in an investigational drug study or history of receiving any
             investigational treatment within 14 days prior to screening for this study, except for
             testosterone-lowering therapy in men with prostate cancer.

         16. Assessed by the Investigator to be unable or unwilling to comply with the requirements
             of the protocol.

         17. Concurrent participation in any interventional clinical trial.

         18. Pregnant and nursing women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological Complete Response Rate
Time Frame:8 months
Safety Issue:
Description:Compare the efficacy of the NANT neoadjuvant TNBC Vaccine treatment vs standard-of-care (SoC) therapy as assessed by pathologic complete response (pCR) rate in the breast and axilla.

Secondary Outcome Measures

Measure:Evaluation of safety as determined by incidence or treatment-emergent adverse events
Time Frame:36 months
Safety Issue:
Description:Incidence of treatment -emergent adverse events
Measure:Evaluate additional measures of efficacy by event-free survival
Time Frame:36 months
Safety Issue:
Description:Time from randomization to first occurrence of advancement of disease
Measure:Overall survival
Time Frame:36 months
Safety Issue:
Description:Time from date of first treatment to death from any cause
Measure:Locoregional relapse
Time Frame:36 months
Safety Issue:
Description:Presence of any disease recurrence, including location
Measure:Distant metastatic rates at 1 year
Time Frame:36 months
Safety Issue:
Description:Number of patients with a metastatic lesion

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NantKwest, Inc.

Trial Keywords

  • TNBC

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