- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03563157
QUILT 3.071: NANT Colorectal Cancer (CRC) Vaccine
NANT Colorectal Cancer (CRC) Vaccine: A Phase 1b/2 Trial of the NANT CRC Vaccine vs Regorafenib in Subjects With Metastatic CRC Who Have Been Previously Treated With Standard-of-Care Therapy
Study Overview
Status
Conditions
Intervention / Treatment
- Biological: ETBX-011
- Biological: Aldoxorubicin Hydrochloride
- Biological: ALT-803
- Biological: ETBX-021
- Biological: ETBX-051
- Biological: ETBX-061
- Biological: GI-4000
- Biological: GI-6207
- Biological: GI-6301
- Biological: haNK
- Drug: Avelumab
- Drug: Capecitabine
- Drug: Cetuximab
- Drug: Cyclophosphamide
- Drug: 5-Fluorouracil
- Drug: Leucovorin
- Drug: Nab-paclitaxel
- Drug: Oxaliplatin
- Drug: Regorafenib
- Procedure: SBRT
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
El Segundo, California, United States, 90245
- Chan Soon-Shiong Institute for Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years.
- Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
- Histologically-confirmed recurrent or metastatic CRC previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy; or subjects who are ineligible for these therapies.
- ECOG performance status of 0 or 1.
- Have at least 1 measurable lesion of ≥ 1.0 cm.
- Must have a recent 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.
- Must be willing to provide blood samples prior to the start of treatment on this study for prospective tumor molecular profiling and exploratory analyses.
- 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.
- 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 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.
Phase 2 single-arm component only
- Must have progressed on or after regorafenib treatment in the randomized phase 2 portion of the study OR progressed or experienced unacceptable toxicity on SoC and regorafenib prior to enrollment on the study.
Exclusion Criteria:
- MSI-high or MMR-deficient tumors eligible for, but not yet treated with, a PD-1 inhibitor.
- Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drugs 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, or autoimmune disease associated with lymphoma).
- History of organ transplant requiring immunosuppression.
- History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
Inadequate organ function, evidenced by the following laboratory results:
- ANC < 1,000 cells/mm^3.
- Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL)
- Platelet count < 75,000 cells/mm^3.
- Total bilirubin > ULN (unless the subject has documented Gilbert's syndrome).
- AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
- ALP > 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.
- Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.
- 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.
- Serious myocardial dysfunction defined by ECHO as absolute LVEF 10% below the institution's lower limit of predicted normal.
- Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
- Positive results of screening test for HIV.
- 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.
- 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.
- Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
- Participation in an investigational drug study or history of receiving any investigational treatment within 30 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.
Phase 2 randomized component only
- Prior regorafenib treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NANT Colorectal Cancer (CRC) Vaccine
A combination of agents will be administered to subjects in this study: Aldoxorubicin HCI, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, Avelumab, Capecitabine, Cetuximab, Cyclophosphamide, 5-Fluorouracil, Leucovorin, Nab-paclitaxel, Oxaliplatin, Regorafenib, SBRT.
|
Ad5 [E1-, E2b-]-CEA
Aldoxorubicin Hydrochloride HCI
Recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D;IL-15RaSu/IgG1 Fe complex1]
Ad5 [E1-, E2b-]-[HER2]
Ad5 [E1-, E2b-]-Brachyury
Ad5 [E1-, E2b-]-mucin 1 [MUC1]
RAS yeast
CEA yeast
Brachyury yeast
haNK™, NK-92 [CD16.158V,
ER IL-2]
BAVENCIO® injection
XELODA® tablets
ERBITUX® injection
Cyclophosphamide Capsules
5-FU; Fluorouracil Injection
Leucovorin Calcium
ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles for injectable suspension] [albumin-bound]
ELOXATIN® injection
STIVARGA® tablets
Stereotactic body radiation therapy
|
Active Comparator: Regorafenib
In subjects with metastatic CRC who have been previously treated with standard-of-care (SOC) therapy.
|
STIVARGA® tablets
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version 4.03
Time Frame: 2 years
|
Phase 1b
|
2 years
|
Progression Free Survival from baseline to progression, per RECIST 1.1
Time Frame: 2 years
|
Phase 2 Randomized Component
|
2 years
|
Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete Response per RECIST 1.1
Time Frame: 1 year
|
Phase 2 Single Arm Component
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ORR for Phase 1b and Phase 2 Randomized Component
Time Frame: 1 year
|
Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete response per RECIST 1.1 and irRC
|
1 year
|
PFS for Phase 1b and Phase 2 Single Arm Component
Time Frame: 2 years
|
Progression Free Survival from baseline to progression per RECIST 1.1 and irRC
|
2 years
|
OS for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component
Time Frame: 2 years
|
Overall Survival from first treatment to date of death (any cause)
|
2 years
|
DOR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component
Time Frame: 2 years
|
Duration of Response from date of first response to date of disease progression or death (any cause), per RECIST 1.1 and irRC
|
2 years
|
DCR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component
Time Frame: 1 year
|
Disease Control Rate: the number of patients with a CR, PR or SD lasting at least 2 months per RECIST 1.1 and irRC
|
1 year
|
QoL for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component
Time Frame: 2 years
|
Quality of Life as assessed by Patient Reported Outcomes using the FACT-C questionnaire
|
2 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Cyclophosphamide
- Paclitaxel
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Leucovorin
- Avelumab
- Cetuximab
Other Study ID Numbers
- QUILT-3.071
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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