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QUILT-3.080: NANT Pancreatic Cancer Vaccine

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ClinicalTrials.gov Identifier: NCT03586869
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
NantKwest, Inc.

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 (SoC) chemotherapy.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Aldoxorubicin HCl Biological: ALT-803 Biological: ETBX-011 Biological: ETBX-021 Biological: ETBX-051 Biological: ETBX-061 Biological: GI-4000 Biological: GI-6207 Biological: GI-6301 Biological: haNK for infusion Biological: bevacizumab Drug: Capecitabine Drug: Cyclophosphamide Drug: Fluorouracil Drug: Leucovorin Drug: nab-Paclitaxel Drug: Oxaliplatin Biological: Avelumab Procedure: SBRT Phase 1 Phase 2

Detailed Description:
Treatment will be administered in two phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws 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 who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's discretion. 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 corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 173 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: QUILT-3.080: Phase 1B/2 Trial Of The NANT Pancreatic Cancer Vaccine As Treatment For Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-Of-Care Therapy
Actual Study Start Date : July 28, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NANT Pancreatic Cancer Vaccine
A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, ALT-803, ETBX-011 (CEA), ETBX-021 (HER2), ETBX-051 (Brachyury), ETBX-061 (MUC1), GI-4000, GI-6207, GI-6301, haNK for infusion, avelumab, bevacizumab, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, oxaliplatin, and Stereotactic Body Radiation Therapy (SBRT).
Drug: Aldoxorubicin HCl
Aldoxorubicin Hydrochloride

Biological: ALT-803
Recombinant human super agonist interleukin-15 (IL-15) complex

Biological: ETBX-011
Ad5 [E1-, E2b-]-CEA

Biological: ETBX-021
Ad5 [E1-, E2b-]-HER2

Biological: ETBX-051
Ad5 [E1-, E2b-]-Brachyury

Biological: ETBX-061
Ad5 [E1-, E2b-]-MUC1

Biological: GI-4000
RAS yeast

Biological: GI-6207
Carcinoembryonic Antigen (CEA) yeast

Biological: GI-6301
Brachyury yeast

Biological: haNK for infusion
NK-92 [CD16.158V, ER IL-2]

Biological: bevacizumab
Recombinant human anti-Vascular Endothelial Growth Factor (VEGF) IgG1 monoclonal

Drug: Capecitabine
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine

Drug: Cyclophosphamide
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

Drug: 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

Drug: Oxaliplatin
cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum

Biological: Avelumab
Recombinant human anti-programmed death-ligand 1 (PD-L1) IgG1 monoclonal antibody

Procedure: SBRT
Stereotactic Body Radiation Therapy




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (AEs), graded using the NCI CTCAE Version 4.03 [ Time Frame: 2 years ]
    Phase 1b Primary Outcome

  2. Incidence of treatment-emergent serious adverse events (SAEs), graded using the NCI CTCAE Version 4.03 [ Time Frame: 2 years ]
    Phase 1b Primary Outcome

  3. Overall Response Rate by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 2 Primary Outcome


Secondary Outcome Measures :
  1. ORR by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 1b Secondary Outcome


Other Outcome Measures:
  1. Overall Response Rate by immune-related Response Criteria (irRC) [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  2. Progression Free Survival by RECIST Version 1.1 [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  3. Progression Free Survival by irRC [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  4. Overall Survival [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  5. Duration Of Response by RECIST Version 1.1 and irRC [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  6. Disease Control Rate (confirmed CR, PR, or stable disease [SD] lasting for at least 2 months) by RECIST and irRC [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome

  7. Quality of Life by patient-reported outcomes (PROs) [ Time Frame: 2 years ]
    Phase 1b and 2 Secondary Outcome



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Age ≥ 18 years old.
  2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
  3. Histologically-confirmed pancreatic adenocarcinoma with progression on or after SoC therapy.
  4. ECOG performance status of 0 to 2.
  5. Have at least 1 measurable lesion of ≥ 1.0 cm.
  6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment 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. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
  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. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
  9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
  10. 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, 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, autoimmune disease associated with lymphoma).
  3. History of organ transplant requiring immunosuppression.
  4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
  5. Inadequate organ function, evidenced by the following laboratory results:

    1. Absolute neutrophil count < 1,000 cells/mm3.
    2. Platelet count < 75,000 cells/mm3.
    3. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
    4. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    5. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
    6. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
    7. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.
    8. Medically uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
  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. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
  7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (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 initiation of treatment on this study, except for receipt of testosterone-lowering therapy in men with prostate cancer, or treatment with any NANT Cancer Vaccine therapy.
  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.

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): NCT03586869


Contacts
Contact: NantKwest Clinical Review Team 800-988-6083 clinical.trials@NantKwest.com

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

Responsible Party: NantKwest, Inc.
ClinicalTrials.gov Identifier: NCT03586869     History of Changes
Other Study ID Numbers: QUILT-3.080
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 2018
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
Albumin-Bound Paclitaxel
Doxorubicin
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