Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
2 other identifiers
interventional
11
1 country
1
Brief Summary
Background: ETBX-011, ETBX-061, and ETBX-051 are cancer vaccines. Their goal is to teach the immune system to target and kill cancer cells. The vaccines target 3 proteins found in many types of cancer. Researchers think targeting all 3 proteins in unison will have the best results. Objective: To test the safety of combining ETBX-011, ETBX-061, and ETBX-051 and their effects on the immune system. Eligibility: People ages 18 and older with advanced cancer that has not responded to standard therapies Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Scan: They will lie in a machine that takes pictures of the body. Participants will receive the 3 vaccines through 3 shots under the skin every 3 weeks for 3 doses, then every 8 weeks for up to 1 year. They will have blood and urine tests at each vaccine visit. They will have scans and other measurements of their tumor after 9 weeks and then at their vaccine visits every 8 weeks. Participants will keep a diary of symptoms at the injection site. Participants will have a visit 90 days after their final treatment. This will include a physical exam and blood and urine tests. If they have any ongoing side effects, they will be followed until these end or are not changing. After this visit, they will be called every 3 months for the first year, every 6 months for the next 2 years, then every 12 months for another 2 years to see how they are doing. Participants will have the option to enroll in a long-term follow-up study. ...
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2018
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 23, 2017
CompletedFirst Posted
Study publicly available on registry
December 27, 2017
CompletedStudy Start
First participant enrolled
January 31, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 22, 2018
CompletedResults Posted
Study results publicly available
December 23, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 24, 2020
CompletedSeptember 9, 2020
August 1, 2020
4 months
December 23, 2017
October 25, 2019
August 25, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Serious and Non-serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Date treatment consent signed to date off study, approximately 16 months and 6 days.
Recommended Phase 2 Dose (RP2D)
RP2D is defined as ≤ 1 of 6 of the initial 6 subjects who experience a dose limiting toxicity (DLT), than this dose level will be defined as the RP2D. A DLT is defined as any Grade 3 or greater toxicity that is possibly related to the vaccine and as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 with the exception of transient (≤ 24 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical management (≤ 24 hours) Grade 3 fatigue, skin reactions or rash, headache, nausea, emesis that resolves to Grade ≤ 1 or asymptomatic grade 3 amylase/lipase elevation.
RP2D was based upon evaluation of DLTs. Participants were followed for DLTs from the first dose of vaccine for 3 weeks.
Secondary Outcomes (4)
Number of Participants Who Achieve an Objective Confirmed Complete or Partial Response Assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Approximately 3.5 months
Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months
up to 6 months
Progression-free Survival (PFS)
up to 12 months
Overall Survival (OS)
up to 12 months
Other Outcomes (4)
Number of Participants With a Positive Mucin-1 (MUC-1) Specific T-Cells Immune Response
up to week 6
Number of Participants With a Positive Carcinoembryonic Antigen (CEA) Specific T-Cells Immune Response
up to week 6
Number of Participants With a Positive Brachyury Specific T-Cells Immune Response
up to week 6
- +1 more other outcomes
Study Arms (2)
1/Arm 1-Dose De-Escalation
EXPERIMENTALDose De-Escalation
2/Arm 2 - Dose Expansion
EXPERIMENTALDose Expansion
Interventions
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Eligibility Criteria
You may qualify if:
- Age greater than or equal to 18 years (male and female).
- Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)'s guidelines.
- Subjects with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancy.
- Subjects must have completed or had disease progression on at least one prior line of disease-appropriate therapy or not be candidates for therapy of proven efficacy for their disease.
- Subjects may have measurable or non-measurable but evaluable. Subjects with surgically resected locally advanced or metastatic disease at high risk of relapse are also eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.
- Subjects who have received prior carcinoembryonic antigen (CEA), mucin-1 (MUC1), and/or Brachyury-targeted immunotherapy (vaccine) are eligible for this trial if this treatment was discontinued at least 4 weeks prior to enrollment.
- Resolution of clinically significant side effects of prior chemotherapy, radiotherapy, immunotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) Grade less than or equal to 1 or grade less than or equal to 2 for neuropathy.
- Adequate hematologic function at screening, as follows:
- Absolute neutrophil count (ANC) \>= 1 x 10\^9/L
- Hemoglobin \>= 9 g/dL
- Platelets \>= 75,000/mcL.
- Adequate renal and hepatic function at screening, as follows:
- Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) \>= 40 mL/min (if using the Cockcroft-Gault formula below):
- Female CrCl = ((140 - age in years) x weight in kg x 0.85) / (72 x serum creatinine in mg/dL)
- +5 more criteria
You may not qualify if:
- Pregnant and nursing women. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with combination ETBX-011, ETBX-051, ETBX-061, breastfeeding should be discontinued if the mother is treated with combination ETBX-011, ETBX-051, ETBX-061. These potential risks may also apply to other agents used in this study.
- There should be a minimum of 4 weeks from any prior investigational drug, chemotherapy, immunotherapy, with the exception of hormonal therapy for prostate and breast cancers, human epidermal growth factor receptor 2 (HER2-) directed therapy for HER2+ breast or stomach cancer (3+ immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH+), drugs targeting epidermal growth factor receptor (EGFR), anaplastic large-cell lymphoma kinase (ALK) or ROS1 in EGFR,ALK, ROS1-mutated lung cancer, respectively, or standard maintenance therapies for any solid tumor under the condition that subjects are on these therapies for at least two months before start of trial treatment.
- There should also be a minimum of 4 weeks from any prior radiotherapy except for palliative bone directed therapy.
- Known active brain or central nervous system metastasis (less than 1 month out from definitive radiotherapy or surgery), or seizures requiring anticonvulsant treatment, or clinically significant cerebrovascular accident or transient ischemic attack (\<3 months).
- Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment.
- Subjects with clinically significant heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (\< 1 year) of ventricular arrhythmia.
- Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures.
- History of second malignancy within 3 years prior to enrollment except for the following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer or other localized malignancy after discussion with the medical monitor.
- Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by hepatitis B surface antigen (HBsAg) and hepatitis C serology).
- Subjects on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (less than or equal to the equivalent of prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 2 weeks prior to enrollment for recent short course use (less than or equal to 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (\> 14 days). In addition, the use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study.
- Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded.
- Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.
- Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist(R)) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX(R), Fluzone(R)) within 28 days or 14 days, respectively, of the first planned dose of ETBX vaccine.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (4)
Balint JP, Gabitzsch ES, Rice A, Latchman Y, Xu Y, Messerschmidt GL, Chaudhry A, Morse MA, Jones FR. Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer. Cancer Immunol Immunother. 2015 Aug;64(8):977-87. doi: 10.1007/s00262-015-1706-4. Epub 2015 May 9.
PMID: 25956394BACKGROUNDMorse MA, Chaudhry A, Gabitzsch ES, Hobeika AC, Osada T, Clay TM, Amalfitano A, Burnett BK, Devi GR, Hsu DS, Xu Y, Balcaitis S, Dua R, Nguyen S, Balint JP Jr, Jones FR, Lyerly HK. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013 Aug;62(8):1293-301. doi: 10.1007/s00262-013-1400-3. Epub 2013 Apr 30.
PMID: 23624851BACKGROUNDGabitzsch ES, Tsang KY, Palena C, David JM, Fantini M, Kwilas A, Rice AE, Latchman Y, Hodge JW, Gulley JL, Madan RA, Heery CR, Balint JP Jr, Jones FR, Schlom J. The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic. Oncotarget. 2015 Oct 13;6(31):31344-59. doi: 10.18632/oncotarget.5181.
PMID: 26374823BACKGROUNDGatti-Mays ME, Redman JM, Donahue RN, Palena C, Madan RA, Karzai F, Bilusic M, Sater HA, Marte JL, Cordes LM, McMahon S, Steinberg SM, Orpia A, Burmeister A, Schlom J, Gulley JL, Strauss J. A Phase I Trial Using a Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury)-Based Immunotherapy Vaccine Regimen in Patients with Advanced Cancer. Oncologist. 2020 Jun;25(6):479-e899. doi: 10.1634/theoncologist.2019-0608. Epub 2019 Oct 8.
PMID: 31594913RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Julius Y. Strauss
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Julius Y Strauss, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- National Cancer Institute
Study Record Dates
First Submitted
December 23, 2017
First Posted
December 27, 2017
Study Start
January 31, 2018
Primary Completion
May 22, 2018
Study Completion
August 24, 2020
Last Updated
September 9, 2020
Results First Posted
December 23, 2019
Record last verified: 2020-08
Data Sharing
- IPD Sharing
- Will not share