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QUILT-3.049: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03175666
Recruitment Status : Withdrawn (Trial not initiated)
First Posted : June 5, 2017
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
NantKwest, Inc.

Tracking Information
First Submitted Date  ICMJE May 31, 2017
First Posted Date  ICMJE June 5, 2017
Last Update Posted Date August 29, 2019
Estimated Study Start Date  ICMJE December 2017
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2017)
  • 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 ]
    Phase 1b primary endpoint (safety)
  • Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by RECIST)
  • ORR by Immune-related response criteria (irRC ) [ Time Frame: 1 year ]
    Phase 2 primary endpoint (ORR by irRC)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2017)
  • ORR by RECIST Version 1.1 [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by RECIST)
  • ORR by irRC [ Time Frame: 1 year ]
    Phase 1b secondary endpoint (ORR by irRC)
  • Progression-free survival (PFS) by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by RECIST)
  • PFS by irRC [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PFS by irRC)
  • Overall survival (OS): time from the date of first treatment to the date of death (any cause) [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (OS)
  • 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 ]
    Phase 1b and 2 secondary endpoint (DR)
  • Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months [ Time Frame: 2 months ]
    Phase 1b and 2 secondary endpoint (DCR)
  • Patient-reported outcomes (PRO) using the Functional Assessment of Cancer Therapy (FACT) Breast Symptom Index (FBSI) questionnaire [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (PRO)
  • Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint (AEs)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE QUILT-3.049: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy
Official Title  ICMJE NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer
Intervention  ICMJE
  • Biological: avelumab
    Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
  • Biological: bevacizumab
    Recombinant human anti-VEGF IgG1 monoclonal antibody
  • Drug: capecitabine
    5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
  • Drug: cisplatin
    (SP-4-2)-diamminedichloroplatinum(II)
  • Drug: cyclophosphamide
    2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
  • Drug: 5-Fluorouracil
    5-fluoro-2,4 (1H,3H)-pyrimidinedione
  • Drug: Leucovorin
    Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)
  • Drug: nab-paclitaxel
    5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
  • Drug: Lovaza
    omega-3-acid ethyl esters)
  • Radiation: Stereotactic Body Radiation Therapy
    (SBRT)
  • Biological: ALT-803
    recombinant human super agonist interleukin-15 (IL-15) complex
  • Biological: ETBX-011
    adenovirus serotype-5 [Ad5] [E1-, E2b-]-CEA (carcinoembryonic antigen)
  • Biological: ETBX-051
    Ad5 [E1-, E2b-]-Brachyury
  • Biological: ETBX-061
    Ad5 [E1-, E2b-]-mucin 1 (MUC1)
  • Biological: GI-4000
    RAS yeast vaccine
  • Biological: GI-6207
    CEA yeast vaccine
  • Biological: GI-6301
    Brachyury yeast vaccine
  • Biological: haNK
    NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion (haNK™ for Infusion)
Study Arms  ICMJE Experimental: Nant TNBC
avelumab, 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.
Interventions:
  • Biological: avelumab
  • Biological: bevacizumab
  • Drug: capecitabine
  • Drug: cisplatin
  • Drug: cyclophosphamide
  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
  • Drug: nab-paclitaxel
  • Drug: Lovaza
  • Radiation: Stereotactic Body Radiation Therapy
  • Biological: ALT-803
  • Biological: ETBX-011
  • Biological: ETBX-051
  • Biological: ETBX-061
  • Biological: GI-4000
  • Biological: GI-6207
  • Biological: GI-6301
  • Biological: haNK
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 27, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2017)
79
Estimated Study Completion Date  ICMJE March 2019
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03175666
Other Study ID Numbers  ICMJE QUILT-3.049
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party NantKwest, Inc.
Study Sponsor  ICMJE NantKwest, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account NantKwest, Inc.
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP