Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

QUILT-3.039: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

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: NCT03136406
Recruitment Status : Active, not recruiting
First Posted : May 2, 2017
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
NantKwest, Inc.

Tracking Information
First Submitted Date  ICMJE April 19, 2017
First Posted Date  ICMJE May 2, 2017
Last Update Posted Date September 14, 2018
Actual Study Start Date  ICMJE August 14, 2017
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03. [ Time Frame: 8 weeks ]
    Phase 1b primary endpoint
  • Objective response rate by RECIST [ Time Frame: 1 year ]
    Phase 2 primary endpoint
  • Objective response rate by irRC [ Time Frame: 1 year ]
    Phase 2 primary endpoint
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03136406 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2017)
  • Objective response rate by RECIST [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Objective response rate by irRC [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Progression-free survival by RECIST during Phase 1b [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Progression-free survival by irRC during Phase 1b [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Overall survival [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 8 weeks ]
    Phase 1b secondary endpoint
  • Progression-free survival by RECIST during Phase 2 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Progression-free survival by irRC during Phase 2 [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Overall survival [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Duration of response [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months). [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Patient-reported outcomes of pancreatic cancer symptoms [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
  • Incidence of treatment-emergent AEs, SAEs, graded using the NCI CTCAE Version 4.03. [ Time Frame: 1 year ]
    Phase 2 secondary endpoint
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-3.039: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
Official Title  ICMJE NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy
Brief Summary This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with pancreatic cancer who have progressed on or after previous Standard of Care first line therapy and chemotherapy.
Detailed Description Treatment will be administered in two phases. Subjects will continue treatment until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or the investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) will enter phase 2 of the study. Subjects may remain on phase 2 of the study for up to 1 year. Treatment will continue throughout phase 2 until the subject experiences PD or unacceptable toxicity, withdraws consent, or 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 Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Drug: Cyclophosphamide
    2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
  • Drug: Oxaliplatin
    cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum
  • Drug: Capecitabine
    5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
  • Drug: 5-Fluorouracil
    5-fluoro-2,4 (1H,3H)-pyrimidinedione
  • Drug: Leucovorin
    L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt
  • Drug: nab-paclitaxel
    Benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-y1ester,(αR,βS)-(9CI) bound to albumin
  • Biological: bevacizumab
    Recombinant human anti-VEGF IgG1 monoclonal
  • Biological: avelumab
    Recombinant human anti-PD-L1 IgG1 monoclonal antibody
  • Biological: ALT-803
    Recombinant human super agonist interleukin-15 (IL-15) complex
  • Biological: aNK for Infusion
    NK-92 cells
  • Biological: ETBX-011
    Ad5 [E1-, E2b-]-CEA
  • Biological: GI-4000
    Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins
Study Arms  ICMJE Experimental: NANT Pancreatic Cancer Vaccine

A combination of agents will be administered to subjects in this study:

cyclophosphamide, oxaliplatin, capecitabine, fluorouracil, leucovorin, nab-paclitaxel, bevacizumab, avelumab, ALT-803, aNK, GI-4000, and ETBX-011.

Interventions:
  • Drug: Cyclophosphamide
  • Drug: Oxaliplatin
  • Drug: Capecitabine
  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
  • Drug: nab-paclitaxel
  • Biological: bevacizumab
  • Biological: avelumab
  • Biological: ALT-803
  • Biological: aNK for Infusion
  • Biological: ETBX-011
  • Biological: GI-4000
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 4, 2018)
3
Original Estimated Enrollment  ICMJE
 (submitted: April 26, 2017)
80
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
  • Histologically-confirmed pancreatic cancer with progression on or after SoC therapy.
  • ECOG performance status of 0 to 2.
  • Have at least 1 measurable lesion and/or non-measurable disease evaluable according to RECIST Version 1.1.
  • Must have a recent tumor biopsy specimen following the conclusion of the most recent anti-cancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
  • Must be willing to provide blood samples for exploratory analyses.
  • Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  • Agreement to practice effective contraception for female subjects with child-bearing potential and non-sterile males.

Exclusion Criteria:

  • History of persistent grade 2 or higher (CTCAE Version 4.03) hematological toxicity resulting from previous therapy.
  • History of other active malignancies or brain metastasis except: controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); 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); bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature. Subjects with a history of another malignancy must have > 5 years without evidence of disease.
  • 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.
  • Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
  • History of organ transplant requiring immunosuppression.
  • History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  • Requires whole blood transfusion to meet eligibility criteria.
  • Inadequate organ function, evidenced by the following laboratory results:

    • White blood cell (WBC) count < 3,500 cells/mm3
    • Absolute neutrophil count < 1,500 cells/mm3.
    • Platelet count < 100,000 cells/mm3.
    • Hemoglobin < 9 g/dL.
    • Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    • Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    • Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    • Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    • International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
  • 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.
  • Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  • Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  • 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.
  • Known hypersensitivity to any component of the study medication(s).
  • Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications. See Excluded Medications list.
  • 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.
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
  • Concurrent participation in any interventional clinical trial.
  • 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03136406
Other Study ID Numbers  ICMJE QUILT-3.039
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 September 2018

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