NeoplasmsPhase 1NCT03384316
Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
A Phase 1 study testing ETBX-051; adenoviral brachyury vaccine, ETBX-061; adenoviral Mucin-1 (MUC1) vaccine and ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine in people with Neoplasms and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Neoplasms, Prostate Cancer, Lung Cancer
- What is being tested?
- ETBX-051; adenoviral brachyury vaccine, ETBX-061; adenoviral Mucin-1 (MUC1) vaccine and ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2018to 24 Aug 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 20Show fewer
- 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)
- Male CrCl = ((140 - age in years) x weight in kg x 1.00)/ 1.00) / (72 x serum creatinine in mg/dL)
- Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, unless liver metastases are present, then values must be less than or equal to 3 x ULN)
- The effects of the combination ETBX-011, ETBX-051, ETBX-061 vaccine regimen on the developing human fetus are unknown. For this reason, female subjects of childbearing potential defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or who is not postmenopausal (menopause being defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes) and male patients who are not surgically sterile (vasectomy etc.), must agree to use acceptable contraceptive methods for the duration of the study and for one month after the last vaccination. Acceptable forms of contraception include oral contraceptives, intrauterine device, condom or vaginal diaphragm plus spermicidal (gel/foam/cream/vaginal suppository), or total abstinence.
- Ability to attend required study visits and return for adequate follow up, as required by this protocol.
Who cannot join
- 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 active autoimmune disease requiring systemic immunosuppressive treatment within the past 4 weeks such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. A history of autoimmune disease which is not active nor has required recent systemic immunosuppressive therapy (< 4 weeks prior to enrollment) is not reason for exclusion.
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
...
Read the detailed description
Background:
- The overall goal of the current project is to expand our immunotherapeutic approach for the treatment of advanced cancer employing a multi-targeted approach.
- Therapeutic cancer vaccines targeting overexpressed proteins offer a potential method to activate T cells against tumors.
- A novel adenovirus based vaccine targeting three (3) human tumor associated antigens (TAA), carcinoembryonic antigen (CEA), mucin-1 (MUC1), and brachyury, respectively has demonstrated anti-tumor cytolytic T cell responses in pre-clinical animal models of cancer.
Objectives:
-To determine the overall safety and recommended phase 2 dose of a combination of three immunotherapeutic vaccines (ETBX-011/ETBX-061/ETBX-051), when administered subcutaneously (SC) to subjects with advanced solid tumors
Eligibility:
- Subjects age 18 and older with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancy who have completed or had disease progression on at least one prior line of disease-appropriate therapy or who are not candidates for therapy of proven efficacy for their disease.
- Subjects may have measurable or non-measurable but evaluable disease. Subjects with surgically resected metastatic disease at high risk of relapse are also eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
- Adequate organ and bone marrow function
- Subjects with active autoimmune diseases requiring systemic treatment and subjects requiring systemic steroids (except for physiologic doses for steroid replacement) are not allowed
Design:
- This is a Phase I trial in subjects with advanced cancer. A combination of three therapeutic vaccines (ETBX-011, ETBX-51, EBX-61) using the same modified Adenovirus vector backbone, separately encoding three well-studied tumor-associated antigens will be assessed. The vaccine will be tested at a single dose level, and a dose de-escalation design (if required). The dose level of each vaccine tested will be 5x1011 VP. This dose has been found in prior phase 1 testing of Ad5 [E1-, E2b-]-CEA(6D) (ETBX-011) to be well tolerated (with no dose-limiting toxicities (DLTs) or related Serious adverse events (SAEs), and optimal for induction of immune responses. Each of the three vaccines will be administered subcutaneously (SC) at separate injection sites (proximal limb, preferably the thigh), every 3 weeks for 3 doses, then bi-monthly (every 8 week) boosts for up to a year.
- Up to six patients will be enrolled at Dose Level 1. If less than or equal to l of 6 patients experience a DLT, initiation of the dose expansion phase will occur. If greater than or equal to 2 of 6 experience DLT at Dose Level 1, then dose de-escalation will occur. Up to six patients will be enrolled at the lower dose level Dose Level -1 (1x10^11 VP). If less than or equal to 1 of 6 patients experience a DLT, then the maximum tolerated (MTD) will be declared at this dose, and initiation of the dose expansion phase will occur. If greater than or equal to 2 of 6 experience DLT at Dose Level -1, then a protocol amendment may be written to evaluate a further dose de-escalation.
- A dose expansion phase of study will be enrolled after the MTD of the combination vaccine has been determined. An additional 4 subjects will be enrolled in the dose expansion component of the trial, for a total of 10 subjects at the MTD.
- The ETBX-011, ETBX-51 and ETBX-61 vaccines will be administered SC every 3 weeks for 3 doses, and then bi monthly boosts for up to a year. Evaluations including immunological assessments will be carried out at baseline, on days of vaccination, and after the last vaccination.
- Conditions
- Neoplasms, Prostate Cancer, Lung Cancer, Breast Cancer, Colon Cancer
- Being tested
- ETBX-051; adenoviral brachyury vaccine, ETBX-061; adenoviral Mucin-1 (MUC1) vaccine, ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine
- Keywords
- Combination Vaccine, Adenoviral, ETBX-011, ETBX-061, ETBX-051
- Medical subject headings
- Neoplasms, Prostatic Neoplasms, Lung Neoplasms, Breast Neoplasms, Colonic Neoplasms, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ETBX-051; adenoviral brachyury vaccineBiological
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
ETBX-061; adenoviral Mucin-1 (MUC1) vaccineBiological
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccineBiological
immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
| Study group | Role | What they receive |
|---|---|---|
| 1/Arm 1-Dose De-Escalation | Experimental | Dose De-Escalation Receives: Biological: ETBX-051; adenoviral brachyury vaccine; Biological: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine; Biological: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine |
| 2/Arm 2 - Dose Expansion | Experimental | Dose Expansion Receives: Biological: ETBX-051; adenoviral brachyury vaccine; Biological: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine; Biological: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Objective response is determined by participants whose tumors shrunk after therapy assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Approximately 3.5 months
Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (taking as reference the smallest sum diameters while on study).
Measured: up to 6 months
Progression-free Survival (PFS)
The amount of time a subject survives without disease progression after treatment. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm. (Note: the appearance of one or more lesions is also considered progression).
Measured: up to 12 months
Overall Survival (OS)
OS is defined as the amount of time a subject survives after therapy assessed from the date of first treatment to the date of death (any cause).
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start31 Jan 2018
- Primary completion22 May 2018
- Study completion24 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Julius Strauss, M.D., National Cancer Institute (NCI)
- Investigators
- Julius Y Strauss, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03384316
- Sponsor's protocol ID
- 180032
- Other IDs
- 18-C-0032
- Status last verified
- Aug 2020
- First submitted
- 23 Dec 2017
- Last updated
- 9 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25956394Morse 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.
PubMed 23624851Gabitzsch 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.
PubMed 26374823Gatti-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.
PubMed 31594913
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
- ClinicalTrials.gov ID
- NCT03384316
- Acronym / sponsor ID
- 180032
- Conditions
- Neoplasms, Prostate Cancer, Lung Cancer, Breast Cancer, Colon Cancer
- Keywords
- Combination Vaccine, Adenoviral, ETBX-011, ETBX-061, ETBX-051
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 22 May 2018 (actual)
- Study completion
- 24 Aug 2020 (actual)
- First posted
- 27 Dec 2017 (actual)
- Results
- Posted 23 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
Detailed description
Background:
- The overall goal of the current project is to expand our immunotherapeutic approach for the treatment of advanced cancer employing a multi-targeted approach.
- Therapeutic cancer vaccines targeting overexpressed proteins offer a potential method to activate T cells against tumors.
- A novel adenovirus based vaccine targeting three (3) human tumor associated antigens (TAA), carcinoembryonic antigen (CEA), mucin-1 (MUC1), and brachyury, respectively has demonstrated anti-tumor cytolytic T cell responses in pre-clinical animal models of cancer.
Objectives:
-To determine the overall safety and recommended phase 2 dose of a combination of three immunotherapeutic vaccines (ETBX-011/ETBX-061/ETBX-051), when administered subcutaneously (SC) to subjects with advanced solid tumors
Eligibility:
- Subjects age 18 and older with cytologically or histologically confirmed locally advanced or metastatic solid tumor malignancy who have completed or had disease progression on at least one prior line of disease-appropriate therapy or who are not candidates for therapy of proven efficacy for their disease.
- Subjects may have measurable or non-measurable but evaluable disease. Subjects with surgically resected metastatic disease at high risk of relapse are also eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
- Adequate organ and bone marrow function
- Subjects with active autoimmune diseases requiring systemic treatment and subjects requiring systemic steroids (except for physiologic doses for steroid replacement) are not allowed
Design:
- This is a Phase I trial in subjects with advanced cancer. A combination of three therapeutic vaccines (ETBX-011, ETBX-51, EBX-61) using the same modified Adenovirus vector backbone, separately encoding three well-studied tumor-associated antigens will be assessed. The vaccine will be tested at a single dose level, and a dose de-escalation design (if required). The dose level of each vaccine tested will be 5x1011 VP. This dose has been found in prior phase 1 testing of Ad5 [E1-, E2b-]-CEA(6D) (ETBX-011) to be well tolerated (with no dose-limiting toxicities (DLTs) or related Serious adverse events (SAEs), and optimal for induction of immune responses. Each of the three vaccines will be administered subcutaneously (SC) at separate injection sites (proximal limb, preferably the thigh), every 3 weeks for 3 doses, then bi-monthly (every 8 week) boosts for up to a year.
- Up to six patients will be enrolled at Dose Level 1. If less than or equal to l of 6 patients experience a DLT, initiation of the dose expansion phase will occur. If greater than or equal to 2 of 6 experience DLT at Dose Level 1, then dose de-escalation will occur. Up to six patients will be enrolled at the lower dose level Dose Level -1 (1x10^11 VP). If less than or equal to 1 of 6 patients experience a DLT, then the maximum tolerated (MTD) will be declared at this dose, and initiation of the dose expansion phase will occur. If greater than or equal to 2 of 6 experience DLT at Dose Level -1, then a protocol amendment may be written to evaluate a further dose de-escalation.
- A dose expansion phase of study will be enrolled after the MTD of the combination vaccine has been determined. An additional 4 subjects will be enrolled in the dose expansion component of the trial, for a total of 10 subjects at the MTD.
- The ETBX-011, ETBX-51 and ETBX-61 vaccines will be administered SC every 3 weeks for 3 doses, and then bi monthly boosts for up to a year. Evaluations including immunological assessments will be carried out at baseline, on days of vaccination, and after the last vaccination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1-Dose De-Escalation | Experimental | Biological: ETBX-051; adenoviral brachyury vaccine, Biological: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine, Biological: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccineDose De-Escalation |
| 2/Arm 2 - Dose Expansion | Experimental | Biological: ETBX-051; adenoviral brachyury vaccine, Biological: ETBX-061; adenoviral Mucin-1 (MUC1) vaccine, Biological: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccineDose Expansion |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (14 listed)
- 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 active autoimmune disease requiring systemic immunosuppressive treatment within the past 4 weeks such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. A history of autoimmune disease which is not active nor has required recent systemic immunosuppressive therapy (< 4 weeks prior to enrollment) is not reason for exclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ETBX-051; adenoviral brachyury vaccineimmunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year | Biological | 1/Arm 1-Dose De-Escalation, 2/Arm 2 - Dose Expansion |
| ETBX-061; adenoviral Mucin-1 (MUC1) vaccineimmunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year | Biological | 1/Arm 1-Dose De-Escalation, 2/Arm 2 - Dose Expansion |
| ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccineimmunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year | Biological | 1/Arm 1-Dose De-Escalation, 2/Arm 2 - Dose Expansion |
Primary outcome
Number of Participants With Serious and Non-serious Adverse Events
Time frame: Date treatment consent signed to date off study, approximately 16 months and 6 days.
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.
Recommended Phase 2 Dose (RP2D)
Time frame: RP2D was based upon evaluation of DLTs. Participants were followed for DLTs from the first dose of vaccine for 3 weeks.
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.
4 secondary outcomes
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)
Time frame: Approximately 3.5 months
Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months
Time frame: up to 6 months
Progression-free Survival (PFS)
Time frame: up to 12 months
Overall Survival (OS)
Time frame: up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25956394Balint 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.
- Background: PubMed 23624851Morse 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.
- Background: PubMed 26374823Gabitzsch 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.
- Results publication: PubMed 31594913Gatti-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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julius Y Strauss, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ETBX-051; adenoviral brachyury vaccine, ETBX-061; adenoviral Mucin-1 (MUC1) vaccine and ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine in people with Neoplasms and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Serious and Non-serious Adverse Events (time frame: Date treatment consent signed to date off study, approximately 16 months and 6 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03384316, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.