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

This study is currently recruiting participants.
Verified October 2017 by NantKwest, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03136406
First Posted: May 2, 2017
Last Update Posted: October 30, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
NantKwest, Inc.
  Purpose
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.

Condition Intervention Phase
Pancreatic Cancer 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 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NANT Pancreatic Cancer Vaccine: Combination Immunotherapy in Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy

Resource links provided by NLM:


Further study details as provided by NantKwest, Inc.:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 80
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03136406


Contacts
Contact: Saundra L Kirven 919-694-6317 saundra.kirven@nantbio.com

Locations
United States, California
Chan Soon-Shiong Institute for Medicine Recruiting
El Segundo, California, United States, 90245
Sponsors and Collaborators
NantKwest, Inc.
  More Information

Responsible Party: NantKwest, Inc.
ClinicalTrials.gov Identifier: NCT03136406     History of Changes
Other Study ID Numbers: QUILT-3.039
First Submitted: April 19, 2017
First Posted: May 2, 2017
Last Update Posted: October 30, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Vaccines
Cyclophosphamide
Fluorouracil
Paclitaxel
Oxaliplatin
Bevacizumab
Capecitabine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating