HER2+ CancerPhase 1NCT01526473
A Phase I Study To Evaluate The Antitumor Activity And Safety Of AVX901
A Phase 1 study testing AVX901 in people with HER2+ Cancer, run by H. Kim Lyerly at 1 site in United States.
Trial summary
HER2 is a protein that is over expressed in 20-30% of breast cancers. It is also found associated with lung, gastric, ovarian, and pancreatic cancers. Although there are existing therapies that can target HER2, most patients will eventually experience progression of their disease even though their cancer continues to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2+ Cancer
- What is being tested?
- AVX901
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One of the following subgroups of patients with HER2 overexpression as follows:
- Histologically-confirmed breast cancer that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable and/or evaluable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior FDA approved HER2 targeted (e.g. trastuzumab, trastuzumab plus pertuzumab, T-DM1, or lapatinib) (determined by their physician).*
- Prior therapy has at least one of the following stipulations:
- Patients may have received neoadjuvant or adjuvant treatment with prior trastuzumab or lapatinib treatment
- Patients have received a a trastuzumab, trastuzumab + pertuzumab, or T-DM1-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 trastuzumab-based combination therapy.
- Patients have received a lapatinib-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 lapatinib-based combination therapy.
Show all 18Show fewer
- Histologically-confirmed gastric, esophageal, or gastroesophageal adenocarcinoma that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior HER2 targeted therapy for a minimum of 9 weeks duration) (determined by their physician). or with previously documented HER2 over-expressing disease not being currently treated on a HER2 targeted therapy.
- Other histologically confirmed metastatic (stage IV) or locally recurrent (stage III) (7th Edition of the AJCC TNM System) malignancy with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+. Because there are no other malignancies with FDA approved HER2 targeting therapies, no prior HER2 directed therapy will be required for this subgroup. However, patients will have been required to have at least 1 line of therapy with a known survival benefit for their malignancy.
- Adults at least 18 years of age at the time of signing the Informed Consent Form;
- Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits. however, CT scans, bone scans, MUGA, Echocardiogram, EKG,and labs performed as standard of care prior to signing consent can be used to fulfill eligibility requirements if they were performed within 8 weeks of the first dose of AVX901 (for the MUGA or echocardiogram) and within 4 weeksof the first dose of study drug for the remainder of the studies
- Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE (version 4.03) Grade ≤ 1 (with the exception of grade 2 alopecia, grade 2 neuropathy and grade 2 fatigue);
- Karnofsky performance status greater than or equal to 80% or ECOG status of 0 or 1 ;
- Adequate hematologic function: (WBC = 2500 mm3, hemoglobin > 10 mg/dl, platelets > 100,000/mm3);
- Adequate renal and hepatic function (Cr < 2.0 mg/dl; bilirubin < 2 X ULN; AST < 2.5 x ULN, ALT < 2.5 X ULN);
- Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal institutional range (MUGA 50%; ECHO 55%);
- Female patients must be of non child-bearing potential or use effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of AVX901;
- Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol;
- Current therapy with endocrine agents (tamoxifen, raloxifene, torimifene and all aromatase inhibitors) and/or bisphosphonates and/or RANK-ligand inhibitors is permitted.
Who cannot join
- Except for patients on the concurrent HER2 targeted therapy (cohort 2) cohort, patients may not receive cytotoxic chemotherapy, monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection), HER2 targeted therapy such as lapatinib, or radiation therapy in the 3 weeks before the first injection, during the injection period or for at least 2 weeks after the last injection. Patients may have received prior radiation including for brain metastases.
- History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Prior history of autoimmune thyroiditis or vitiligo is permitted.
- Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
- Medical or psychological impediment to probable compliance with the protocol.
- Concurrent or prior second malignancy (within the past 5 years) other than non-melanoma skin cancer, controlled superficial bladder cancer or controlled cervical cancer.
- Presence of active infection or systemic use of antimicrobials within 72 hours prior to the first injection
Show all 9Show fewer
- Patients on steroid therapy (or other immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment (except steroids used as anti-emetics for systemic chemotherapy which are permitted).
- Presence of an active acute or chronic infection including HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections. .
- Pregnant or nursing women
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase I Study To Evaluate The Antitumor Activity And Safety Of DUKE-002-VRP(HUHER2-ECD+TM), An Alphaviral Vector Encoding The HER2 Extracellular Domain And Transmembrane Region, In Patient With Locally Advanced Or Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Cancers Including Breast Cancer
HER2 is a protein that is over expressed in 20-30% of breast cancers. It is also found associated with lung, gastric, ovarian, and pancreatic cancers. Although there are existing therapies that can target HER2, most patients will eventually experience progression of their disease even though their cancer continues to express HER2. Therefore, new approaches are needed for treating tumors that express HER2.
This clinical trial will use an investigational cancer vaccine called HER2 VRP or AVX901. The vaccine is based on a virus called Venezuelan equine encephalitis but it has been changed so it cannot cause active infection. Instead, the virus has been changed so it tells the immune system to attack cancer cells which make HER2.
The objectives of the study are to evaluate the safety of immunization with HER2 VRP in patients with advanced or metastatic malignancies that express HER2, and to test whether immunization will causes a strong immune system attack against the cancer.
Read the detailed description
Metastatic breast cancer continues to account for more than 400,000 deaths yearly with HER2 positive breast cancers representing approximately one third of cases. Despite the efficacy of trastuzumab in HER2 overexpressing breast cancer, progression of metastatic disease is inevitable. Lapatinib, when combined with capecitabine, improves time to progression in those with trastuzumab resistant disease, but lapatinib resistance also develops in the majority of these patients. HER2 overexpression is also reported in lung, gastric, ovarian, and pancreatic cancers, all of which are also in need of improved treatment options. Because HER2 continues to be expressed in patients with refractory disease, using an immune-targeting approach against HER2 remains a promising strategy. A number of clinical trials have confirmed the ability of vaccines to activate T cell and antibody responses against HER2. We propose using a propagation-defective, single-cycle, RNA replicon vector system that expresses HER2 as an antigen-specific cancer vaccine in a Phase I clinical trial in patients with advanced or metastatic malignancies expressing HER2. The vaccine was prepared from an attenuated strain of an alphavirus in which 3 of the 7 viral genes were removed and replaced with a HER2 gene to create a self-amplifying RNA (replicon) that expresses large amounts of HER2. The HER2 gene used includes the extracellular domain (ECD) and transmembrane (TM) regions of HER2 but not the ICD region. The HER2 ECDTM replicon is packaged into virus-like replicon particles (VRP) by providing the alphavirus structural proteins from separate RNA molecules. When VRP are used for immunization, the VRP infect individual cells and the replicon expresses HER2 which then induces an immune response.
The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies. The study will also monitor immune responses to HER2. Preliminary data on tumor response rate will also be collected.
- Conditions
- HER2+ Cancer
- Being tested
- AVX901
- Keywords
- Alphavirus, Vaccine, Immunotherapy, HER2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVX901Biological
Also called VRP-HER2 ECDTM
Dosing will consist of AVX901 at 4 x 10E8 IU intramuscularly, given every 2 weeks for a total of three doses.
| Study group | Role | What they receive |
|---|---|---|
| AVX901 | Experimental | AVX901 at 4 x 108 IU intramuscularly, given every 2 weeks for a total of three doses. Receives: Biological: AVX901 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies
Measured: 3 months
Secondary outcomes (1)
Immune response
The secondary objective of the study HER2 specific response by ELISPOT and ELISA.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionMar 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2+ CancerStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Kim Lyerly
- Sponsor type
- University, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation
- Responsible party
- Sponsor-investigator, H. Kim Lyerly, Duke University
- Investigators
- Michael Morse, MD, Principal investigator, Duke UniversityH. Kim Lyerly, MD, Study director, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526473
- Sponsor's protocol ID
- Pro00034612
- Status last verified
- Mar 2018
- First submitted
- 24 Jan 2012
- Last updated
- 29 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study To Evaluate The Antitumor Activity And Safety Of DUKE-002-VRP(HUHER2-ECD+TM), An Alphaviral Vector Encoding The HER2 Extracellular Domain And Transmembrane Region, In Patient With Locally Advanced Or Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Cancers Including Breast Cancer
- ClinicalTrials.gov ID
- NCT01526473
- Acronym / sponsor ID
- Pro00034612
- Conditions
- HER2+ Cancer
- Keywords
- Alphavirus, Vaccine, Immunotherapy, HER2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- H. Kim LyerlyUniversity, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation
- Study start
- Feb 2012 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 6 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HER2 is a protein that is over expressed in 20-30% of breast cancers. It is also found associated with lung, gastric, ovarian, and pancreatic cancers. Although there are existing therapies that can target HER2, most patients will eventually experience progression of their disease even though their cancer continues to express HER2. Therefore, new approaches are needed for treating tumors that express HER2.
This clinical trial will use an investigational cancer vaccine called HER2 VRP or AVX901. The vaccine is based on a virus called Venezuelan equine encephalitis but it has been changed so it cannot cause active infection. Instead, the virus has been changed so it tells the immune system to attack cancer cells which make HER2.
The objectives of the study are to evaluate the safety of immunization with HER2 VRP in patients with advanced or metastatic malignancies that express HER2, and to test whether immunization will causes a strong immune system attack against the cancer.
Detailed description
Metastatic breast cancer continues to account for more than 400,000 deaths yearly with HER2 positive breast cancers representing approximately one third of cases. Despite the efficacy of trastuzumab in HER2 overexpressing breast cancer, progression of metastatic disease is inevitable. Lapatinib, when combined with capecitabine, improves time to progression in those with trastuzumab resistant disease, but lapatinib resistance also develops in the majority of these patients. HER2 overexpression is also reported in lung, gastric, ovarian, and pancreatic cancers, all of which are also in need of improved treatment options. Because HER2 continues to be expressed in patients with refractory disease, using an immune-targeting approach against HER2 remains a promising strategy. A number of clinical trials have confirmed the ability of vaccines to activate T cell and antibody responses against HER2. We propose using a propagation-defective, single-cycle, RNA replicon vector system that expresses HER2 as an antigen-specific cancer vaccine in a Phase I clinical trial in patients with advanced or metastatic malignancies expressing HER2. The vaccine was prepared from an attenuated strain of an alphavirus in which 3 of the 7 viral genes were removed and replaced with a HER2 gene to create a self-amplifying RNA (replicon) that expresses large amounts of HER2. The HER2 gene used includes the extracellular domain (ECD) and transmembrane (TM) regions of HER2 but not the ICD region. The HER2 ECDTM replicon is packaged into virus-like replicon particles (VRP) by providing the alphavirus structural proteins from separate RNA molecules. When VRP are used for immunization, the VRP infect individual cells and the replicon expresses HER2 which then induces an immune response.
The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies. The study will also monitor immune responses to HER2. Preliminary data on tumor response rate will also be collected.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AVX901 | Experimental | Biological: AVX901AVX901 at 4 x 108 IU intramuscularly, given every 2 weeks for a total of three doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- One of the following subgroups of patients with HER2 overexpression as follows:
- Patients may have received neoadjuvant or adjuvant treatment with prior trastuzumab or lapatinib treatment
- Patients have received a a trastuzumab, trastuzumab + pertuzumab, or T-DM1-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 trastuzumab-based combination therapy.
- Patients have received a lapatinib-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 lapatinib-based combination therapy.
- Histologically-confirmed gastric, esophageal, or gastroesophageal adenocarcinoma that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior HER2 targeted therapy for a minimum of 9 weeks duration) (determined by their physician). or with previously documented HER2 over-expressing disease not being currently treated on a HER2 targeted therapy.
Key exclusion criteria (9 listed)
- Except for patients on the concurrent HER2 targeted therapy (cohort 2) cohort, patients may not receive cytotoxic chemotherapy, monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection), HER2 targeted therapy such as lapatinib, or radiation therapy in the 3 weeks before the first injection, during the injection period or for at least 2 weeks after the last injection. Patients may have received prior radiation including for brain metastases.
- History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Prior history of autoimmune thyroiditis or vitiligo is permitted.
- Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
- Medical or psychological impediment to probable compliance with the protocol.
- Concurrent or prior second malignancy (within the past 5 years) other than non-melanoma skin cancer, controlled superficial bladder cancer or controlled cervical cancer.
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 |
|---|---|---|
| AVX901Also: VRP-HER2 ECDTMDosing will consist of AVX901 at 4 x 10E8 IU intramuscularly, given every 2 weeks for a total of three doses. | Biological | AVX901 |
Primary outcome
Safety
Time frame: 3 months
The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies
1 secondary outcome
Immune response
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
Related trials for HER2+ Cancer
RecruitingPhase 3
Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation
Metastatic Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
A Study of Skipping Radiation Therapy in People With Breast Cancer
HER2-positive Breast Cancer, Breast Cancer
RecruitingPhase 2
Detecting Tumor DNA in the Blood of HR+/HER2-low Metastatic Breast Cancer Patients to Find Candidates for T-DXd Therapy
Breast Cancer Metastatic, Breast Cancer Stage IV
Not yet recruitingPhase 2
Targeting Aurora A Kinase to Overcome Treatment Resistance in Advanced HR+/HER2+ Breast Cancer
HR+/HER2+ Breast Cancer, Metastatic Breast Cancer
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.
Michael Morse, MD principal investigator
Duke University
H. Kim Lyerly, MD study director
Duke University
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 AVX901 in people with HER2+ Cancer, run by H. Kim Lyerly 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 18 inclusion and 9 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 29 Mar 2018. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Mar 2018.