Clinical Trials /

NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy

NCT03175666

Description:

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with metastatic or unresectable TNBC who have progressed on or after anthracycline-based chemotherapy or who have refused anthracycline-based chemotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy
  • Official Title: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.049
  • NCT ID: NCT03175666

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
avelumabNant TNBC
bevacizumabNant TNBC
capecitabineNant TNBC
cisplatinNant TNBC
cyclophosphamideNant TNBC
5-FluorouracilNant TNBC
LeucovorinNant TNBC
nab-paclitaxelNant TNBC
LovazaNant TNBC
ALT-803Nant TNBC
ETBX-011Nant TNBC
ETBX-051Nant TNBC
ETBX-061Nant TNBC
GI-4000Nant TNBC
GI-6207Nant TNBC
GI-6301Nant TNBC
haNKNant TNBC

Purpose

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with metastatic or unresectable TNBC who have progressed on or after anthracycline-based chemotherapy or who have refused anthracycline-based chemotherapy.

Detailed Description

      Treatment will be administered in 2 phases, an induction and a maintenance phase, as
      described below. Subjects will continue induction treatment for up to 1 year or until they
      experience progressive disease (PD) or experience unacceptable toxicity (not correctable with
      dose reduction), withdraw consent, or if the Investigator feels it is no longer in the
      subject's best interest to continue treatment. Those who have a complete response (CR) in the
      induction phase will enter the maintenance phase of the study. Subjects may remain on the
      maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance
      phase until the subject experiences PD or 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
Nant TNBCExperimentalavelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
  • capecitabine
  • cisplatin
  • cyclophosphamide
  • 5-Fluorouracil
  • Leucovorin
  • nab-paclitaxel
  • Lovaza

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years.

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

          3. Histologically confirmed metastatic or unresectable TNBC that has either progressed on
             or after anthracycline-based chemotherapy or subject has refused anthracycline-based
             chemotherapy.

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

          5. Have at least 1 measurable lesion of ≥ 1.5 cm.

          6. Must have a recent tumor biopsy specimen obtained following the conclusion of the most
             recent anticancer treatment. If a historic specimen is not available, the subject must
             be willing to undergo a biopsy during the screening period.

          7. Must be willing to provide blood samples, and, if considered safe by the Investigator,
             a tumor biopsy specimen at 8 weeks after the start of treatment.

          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.

        Exclusion Criteria:

          1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity
             resulting from previous therapy.

          2. Within 5 years prior to first dose of study treatment, any evidence of other active
             malignancies or brain metastasis except controlled basal cell carcinoma; prior history
             of prostate cancer that is not under active systemic treatment (except hormonal
             therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); and
             bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and
             involving the pulmonary vasculature.

          3. 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.

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

          5. History of organ transplant requiring immunosuppression.

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

          7. Requires whole blood transfusion to meet eligibility criteria.

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

               1. White blood cell (WBC) count < 3,500 cells/mm3.

               2. Absolute neutrophil count < 1,500 cells/mm3.

               3. Platelet count < 100,000 cells/mm3.

               4. Hemoglobin < 9 g/dL.

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

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

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

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

               9. International normalized ratio (INR) or activated partial thromboplastin time
                  (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic
                  anti-coagulation).

          9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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.

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

         11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B
             virus (HBV), or hepatitis C virus (HCV).

         12. 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.

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

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

         15. Concurrent or prior use of a strong CYP3A4 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.

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

         17. 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.

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

         19. Concurrent participation in any interventional clinical trial.

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

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Time Frame:1 year
Safety Issue:
Description:Phase 1b primary endpoint (safety)

Secondary Outcome Measures

Measure:ORR by RECIST Version 1.1
Time Frame:1 year
Safety Issue:
Description:Phase 1b secondary endpoint (ORR by RECIST)
Measure:ORR by irRC
Time Frame:1 year
Safety Issue:
Description:Phase 1b secondary endpoint (ORR by irRC)
Measure:Progression-free survival (PFS) by RECIST Version 1.1
Time Frame:2 years
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (PFS by RECIST)
Measure:PFS by irRC
Time Frame:2 years
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (PFS by irRC)
Measure:Overall survival (OS): time from the date of first treatment to the date of death (any cause)
Time Frame:2 years
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (OS)
Measure:Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first
Time Frame:2 years
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (DR)
Measure:Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months
Time Frame:2 months
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (DCR)
Measure:Patient-reported outcomes (PRO) using the Functional Assessment of Cancer Therapy (FACT) Breast Symptom Index (FBSI) questionnaire
Time Frame:2 years
Safety Issue:
Description:Phase 1b and 2 secondary endpoint (PRO)
Measure:Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
Time Frame:1 year
Safety Issue:
Description:Phase 2 secondary endpoint (AEs)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NantKwest, Inc.

Last Updated

October 26, 2017