Squamous Cell Carcinoma of the Head and NeckPhase 1NCT00257738
0804 GCC: MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck
A Phase 1 study testing MAGE-A3 and HPV-16 vaccine in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment of which is associated with significant morbidity. This type of cancer affects 43,000 individuals each year with an estimated survival rate of 50%. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- MAGE-A3 and HPV-16 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Oct 2012
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older
- Biopsy proven progressive, recurrent (post-surgical, radiation therapy, chemotherapy, combination therapy),or metastatic SCC of the head and neck which, in the judgment of the attending physician, is incurable by standard treatment modalities, OR Biopsy proven SCC which the patient is unwilling to have treated with surgery, chemotherapy or radiation therapy
- One or more of the following: -MAGE-A3 positive tumor -HPV 16 positive tumor.
- Laboratory values obtained less than or equal to 30days prior to registration: -Alkaline phosphatase less than or equal to 3x upper normal limit (UNL) -AST less than or equal to 3x UNL -Creatinine less than or equal to 1.5 x UNL -Hemoglobin greater than or equal to 9.0 g/dL -Albumin greater than or equal to 3 mg/dL
- The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.
- The subject must be willing to return to the University of Maryland Medical center for treatment and study related follow up procedures including blood and tumor collections and completion of imaging studies as required by the protocol.
- ECOG performance status 0-2.
- Tumor that is biopsy accessible and measurable. This includes, but is not limited to, open biopsy, endoscopic biopsy, image guided biopsy, core biopsy and fine needle aspiration.
Who cannot join
- Any of the following:
- Known HIV infection, b. Other circumstances (i.e. concurrent use of systemic immunosuppressants and immunocompromising condition) that in the opinion of the physician renders the patient a poor candidate for this trial. c. Patients with ANY malignant or metastatic SCC mass or lesion within the Central Nervous System (CNS). (e.g. Intraparenchymal/ Brain, Intracordal / Spinal Canal, Bony masses or lesions with extension into the CNS parenchyma) d. Patients with ANY malignant or metastatic SCC mass or lesion or a volume of a mass or lesion in a location that in the judgment of the investigator may significantly impair the health of or threaten the patients life, should an Inflammatory Response occur.
- Any of the following prior therapies: Chemotherapy less than or equal to 4 weeks prior to registration Immunotherapy less than or equal to 4 weeks prior to registration Biologic therapy less than or equal to 4 weeks prior to registration Radiation therapy less than or equal to 4 weeks prior to registration
- Any of the following: Pregnant women Nursing women unwilling to stop breastfeeding Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) NOTE:This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation).
- Either of the following: Other active cancer requiring therapy to control the disease History of other malignancy (i.e. excluding disease under study) within 3 years Exceptions to the above include: adequately treated basal cell or squamous cell skin cancer, prostate cancer.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland School of Medicine
Baltimore, Maryland, 21201-1619
About this study
Official title: A Phase 1 Open Label, Dose Escalation Study to Evaluate the Effect of Four Doses of MAGE-A3/HPV 16 Trojan Peptides 0001 and 0002 Administered Subcutaneously in Combination With Montanide and GM-CSF on Immunological Response, Safety, Tolerability, and Preliminary Efficacy in Patients With Squamous Cell Carcinoma of the Head and Neck
Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment of which is associated with significant morbidity. This type of cancer affects 43,000 individuals each year with an estimated survival rate of 50%. A potential treatment alternative for this patient population is the use of peptide-based immunotherapy. This clinical tial will be using a vaccines comprised on the Trojan peptides MAGE-A3 and HPV 16 to treat patients with Squamous Cell Carcinoma of the Head and Neck who have recurrent, progressive or metastatic SCCHN.
Read the detailed description
Squamous Cell Carcinoma of the Head and Neck affects 43,000 individuals in the United States annually with an estimated overall survival rate of 50%. In order to improve both the survival rate and quality of life for patients who develop unresectable disease recurrence, new therapeutic alternatives are mandated. One potential treatment alternative for this patient population is the use of peptide-based immunotherapy. Despite the success fo preclinical studies using peptide vaccines, therapeutic responses in patients have been sporadic. The reasons for failure are multifactorial and include problems with patient selection, a limited number of antigenic targets, and an inability to correlate immunologic response with therapeutic efficacy. Specifically, patients with disseminated SCCHN have defects in antigen processing, presentation and effector mechanisms that limit their ability to respond to T cell based immunotherapy. Additionally, a paucity of antigenic peptide epitopes are defined for SCCHN, and immunologic monitoring does not correlate well with clinical response.
Recently several investigators, including our research team, have identified a high prevalence of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and helper epitopes. Additionally, we have defined a novel method to enhance the immune response to therapeutic peptide vaccines using Trojan complexes composed of CD4 and CD8 T-cell epitopes, connected by furin cleavable linkers.
In order to define the feasibility and safety of these agents in combination with GM-CSF and montanide ISA 51 for the immunotherapy of SCCHN, in this proposed trial, we will screen patients for immunologic competence based on specific eligibility criteria including both antigen and HLA-A2 expression on tumors. In registered patients, we will test the ability of two novel Trojan peptide complexes, composed of MAGE-A3 and human papilloma virus 16 (HPV 16) epitopes, to stimulate antigen-specific CD 4 and CD 8 T-cell responses. Finally, we will correlate immunologic response with cell dose and the generation of both HPV 16 and MAGE-A3 antigen loss and HLA-A2 loss variants on tumors by evaluating patients for: 1) Changes in tumor size by both physical measurement and CT plus PET measurement; 2) Determining what proportions of individuals who achieve a complete response (CR), partial response (PR), or have stable disease (SD); 3) Progression-free survival; 4) Survival. Successful completion of this clinical trial will result in the development of a strong foundation for a Phase II/III clinical trial using HPV 16 and MAGE-A3 Trojan peptides for the immunotherapy of SCCHN.
- Being tested
- MAGE-A3, HPV-16 vaccine
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAGE-A3Biological
Three dose levels of MAGE-A3 vaccine will be tested : 500ug, 1000 ug and 1500 ug
HPV-16 vaccineBiological
Three dose levels of HPV- 16 vaccine will be tested : 500ug, 1000 ug and 1500 ug
| Study group | Role | What they receive |
|---|---|---|
| MAGE -A3 vaccine | Experimental | for those individuals in which tumor tests positive for MAGE-A3 Receives: Biological: MAGE-A3 |
| HPV 16 vaccine | Experimental | for patients with HPV 16 positive tumor Receives: Biological: HPV-16 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants experiencing toxicity
Maximum grade of each toxicity and percentage of patients experiencing toxicity as assessed by CTCAE v4.0
Measured: 2 year
Secondary outcomes (2)
Tumor response
Tumor response as assessed by RECIST
Measured: 4 years
Tumor infiltrating lymphocytes
analysis will be performed to assess the degree of tumor infiltration by lymphocytes per- and post treatment (if possible)
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2005 (estimated)
- Study startNov 2005
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the Head and NeckStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Responsible party
- Sponsor
- Investigators
- Martin J. Edelman, MD, Principal investigator, University of Maryland, Greenebaum Cancer Ctr
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00257738
- Sponsor's protocol ID
- HP-00041372
- Other IDs
- R01DE015324
- Status last verified
- Oct 2019
- First submitted
- 21 Nov 2005
- Last updated
- 17 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open Label, Dose Escalation Study to Evaluate the Effect of Four Doses of MAGE-A3/HPV 16 Trojan Peptides 0001 and 0002 Administered Subcutaneously in Combination With Montanide and GM-CSF on Immunological Response, Safety, Tolerability, and Preliminary Efficacy in Patients With Squamous Cell Carcinoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT00257738
- Acronym / sponsor ID
- HP-00041372
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Study start
- Nov 2005
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 23 Nov 2005 (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.
Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment of which is associated with significant morbidity. This type of cancer affects 43,000 individuals each year with an estimated survival rate of 50%. A potential treatment alternative for this patient population is the use of peptide-based immunotherapy. This clinical tial will be using a vaccines comprised on the Trojan peptides MAGE-A3 and HPV 16 to treat patients with Squamous Cell Carcinoma of the Head and Neck who have recurrent, progressive or metastatic SCCHN.
Detailed description
Squamous Cell Carcinoma of the Head and Neck affects 43,000 individuals in the United States annually with an estimated overall survival rate of 50%. In order to improve both the survival rate and quality of life for patients who develop unresectable disease recurrence, new therapeutic alternatives are mandated. One potential treatment alternative for this patient population is the use of peptide-based immunotherapy. Despite the success fo preclinical studies using peptide vaccines, therapeutic responses in patients have been sporadic. The reasons for failure are multifactorial and include problems with patient selection, a limited number of antigenic targets, and an inability to correlate immunologic response with therapeutic efficacy. Specifically, patients with disseminated SCCHN have defects in antigen processing, presentation and effector mechanisms that limit their ability to respond to T cell based immunotherapy. Additionally, a paucity of antigenic peptide epitopes are defined for SCCHN, and immunologic monitoring does not correlate well with clinical response.
Recently several investigators, including our research team, have identified a high prevalence of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and helper epitopes. Additionally, we have defined a novel method to enhance the immune response to therapeutic peptide vaccines using Trojan complexes composed of CD4 and CD8 T-cell epitopes, connected by furin cleavable linkers.
In order to define the feasibility and safety of these agents in combination with GM-CSF and montanide ISA 51 for the immunotherapy of SCCHN, in this proposed trial, we will screen patients for immunologic competence based on specific eligibility criteria including both antigen and HLA-A2 expression on tumors. In registered patients, we will test the ability of two novel Trojan peptide complexes, composed of MAGE-A3 and human papilloma virus 16 (HPV 16) epitopes, to stimulate antigen-specific CD 4 and CD 8 T-cell responses. Finally, we will correlate immunologic response with cell dose and the generation of both HPV 16 and MAGE-A3 antigen loss and HLA-A2 loss variants on tumors by evaluating patients for: 1) Changes in tumor size by both physical measurement and CT plus PET measurement; 2) Determining what proportions of individuals who achieve a complete response (CR), partial response (PR), or have stable disease (SD); 3) Progression-free survival; 4) Survival. Successful completion of this clinical trial will result in the development of a strong foundation for a Phase II/III clinical trial using HPV 16 and MAGE-A3 Trojan peptides for the immunotherapy of SCCHN.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MAGE -A3 vaccine | Experimental | Biological: MAGE-A3for those individuals in which tumor tests positive for MAGE-A3 |
| HPV 16 vaccine | Experimental | Biological: HPV-16 vaccinefor patients with HPV 16 positive tumor |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 or older
- Biopsy proven progressive, recurrent (post-surgical, radiation therapy, chemotherapy, combination therapy),or metastatic SCC of the head and neck which, in the judgment of the attending physician, is incurable by standard treatment modalities, OR Biopsy proven SCC which the patient is unwilling to have treated with surgery, chemotherapy or radiation therapy
- One or more of the following: -MAGE-A3 positive tumor -HPV 16 positive tumor.
- Laboratory values obtained less than or equal to 30days prior to registration: -Alkaline phosphatase less than or equal to 3x upper normal limit (UNL) -AST less than or equal to 3x UNL -Creatinine less than or equal to 1.5 x UNL -Hemoglobin greater than or equal to 9.0 g/dL -Albumin greater than or equal to 3 mg/dL
- The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.
Key exclusion criteria (6 listed)
- Any of the following:
- Any of the following prior therapies: Chemotherapy less than or equal to 4 weeks prior to registration Immunotherapy less than or equal to 4 weeks prior to registration Biologic therapy less than or equal to 4 weeks prior to registration Radiation therapy less than or equal to 4 weeks prior to registration
- Any of the following: Pregnant women Nursing women unwilling to stop breastfeeding Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) NOTE:This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation).
- Either of the following: Other active cancer requiring therapy to control the disease History of other malignancy (i.e. excluding disease under study) within 3 years Exceptions to the above include: adequately treated basal cell or squamous cell skin cancer, prostate 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 |
|---|---|---|
| MAGE-A3Three dose levels of MAGE-A3 vaccine will be tested : 500ug, 1000 ug and 1500 ug | Biological | MAGE -A3 vaccine |
| HPV-16 vaccineThree dose levels of HPV- 16 vaccine will be tested : 500ug, 1000 ug and 1500 ug | Biological | HPV 16 vaccine |
Primary outcome
Number of participants experiencing toxicity
Time frame: 2 year
Maximum grade of each toxicity and percentage of patients experiencing toxicity as assessed by CTCAE v4.0
2 secondary outcomes
Tumor response
Time frame: 4 years
Tumor infiltrating lymphocytes
Time frame: 4 years
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 17 Oct 2019.
Related trials for Squamous Cell Carcinoma of the Head and Neck
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
A Single Arm Phase II Trial in p16-positive Oropharynx Cancer of Selective Dose De-escalation of nodAl VolumEs at Minimal Risk and Primary Site Disease (SAVED)
Head and Neck Cancer, Head and Neck Squamous Cell Cancer
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
Martin J. Edelman, MD principal investigator
University of Maryland, Greenebaum Cancer Ctr
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 MAGE-A3 and HPV-16 vaccine in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Maryland, Baltimore 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 8 inclusion and 6 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 17 Oct 2019. 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?
Number of participants experiencing toxicity (time frame: 2 year). 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 17 Oct 2019.