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QUILT-3.050: NANT Colorectal Cancer (CRC) Vaccine: Combination Immunotherapy in Subjects With Recurrent or Metastatic CRC

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ClinicalTrials.gov Identifier: NCT03169777
Recruitment Status : Withdrawn (Trial not initiated)
First Posted : May 30, 2017
Last Update Posted : August 27, 2019
Sponsor:
Information provided by (Responsible Party):
NantKwest, Inc.

Tracking Information
First Submitted Date  ICMJE May 25, 2017
First Posted Date  ICMJE May 30, 2017
Last Update Posted Date August 27, 2019
Estimated Study Start Date  ICMJE August 2018
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 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 Complete list of historical versions of study NCT03169777 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 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 year ]
    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)
  • Quality of life (QoL) by patient-reported outcome using the Functional Assessment of Cancer Therapy-Colorectal Cancer (FACT-C) questionnaire [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (QoL)
  • 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
 (submitted: May 25, 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 year ]
    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 years ]
    Phase 1b and 2 secondary endpoint (DCR)
  • Quality of life (QoL) by patient-reported outcome using the Functional Assessment of Cancer Therapy-Colorectal Cancer (FACT-C) questionnaire [ Time Frame: 2 years ]
    Phase 1b and 2 secondary endpoint (QoL)
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE QUILT-3.050: NANT Colorectal Cancer (CRC) Vaccine: Combination Immunotherapy in Subjects With Recurrent or Metastatic CRC
Official Title  ICMJE NANT Colorectal Cancer (CRC) Vaccine: Combination Immunotherapy in Subjects With Recurrent or Metastatic CRC
Brief Summary This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with recurrent and metastatic CRC.
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 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 in 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 Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: avelumab
    Fully human anti-programmed death-ligand 1 (PD-L1) immunoglobulin (Ig)G1 lambda monoclonal antibody
  • Biological: bevacizumab
    Recombinant human anti-vascular endothelial growth factor (VEGF) IgG1 monoclonal antibody
  • Drug: capecitabine
    5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
  • Biological: cetuximab
    Recombinant human/mouse chimeric anti-epidermal growth factor receptor (EGFR) IgG1 monoclonal antibody
  • Drug: Cyclophosphamide
    2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
  • Drug: 5-Fluorouracil (5-FU)
    5-fluoro-2,4 (1H,3H)-pyrimidinedione
  • Drug: fulvestrant
    7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol
  • 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
  • Biological: nivolumab
    Human anti-programmed cell death protein 1 (PD-1) IgG4 kappa monoclonal antibody
  • Drug: Lovaza
    Omega-3-acid ethyl esters
  • Drug: oxaliplatin
    cis-[(1 R,2 R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)- O,O'] platinum
  • 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-]-carcinoembryonic antigen [CEA] vaccine
  • Biological: ETBX-021
    Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine
  • Biological: ETBX-051
    Ad5 [E1-, E2b-]-Brachyury vaccine
  • Biological: ETBX-061
    Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine
  • 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
Study Arms  ICMJE Experimental: Nant CRC Vaccine
avelumab, bevacizumab, capecitabine, cetuximab, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, nab paclitaxel, nivolumab, lovaza, oxaliplatin, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Interventions:
  • Biological: avelumab
  • Biological: bevacizumab
  • Drug: capecitabine
  • Biological: cetuximab
  • Drug: Cyclophosphamide
  • Drug: 5-Fluorouracil (5-FU)
  • Drug: fulvestrant
  • Drug: leucovorin
  • Drug: nab paclitaxel
  • Biological: nivolumab
  • Drug: Lovaza
  • Drug: oxaliplatin
  • Radiation: Stereotactic Body Radiation Therapy
  • 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
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 23, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 25, 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 IRB or IEC guidelines.
  3. Histologically confirmed recurrent or metastatic CRC.
  4. 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 an 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 for controlled basal cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, and cervical); prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable 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, and autoimmune disease associated with lymphoma)
  5. History of organ transplant requiring immunosuppression.
  6. History of or active inflammatory bowel disease (eg, Crohn's disease and ulcerative colitis).
  7. Requires whole blood transfusion to meet eligibility criteria.
  8. Inadequate organ function, evidenced by the following laboratory results:

    1. WBC count < 2,500 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 ULN (unless the subject has documented Gilbert's syndrome).
    6. AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
    7. ALP 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. INR, aPTT, or 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 HIV, HBV, or 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 NCT03169777
Other Study ID Numbers  ICMJE QUILT-3.050
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