Cancer of Head and NeckPhase 1/2NCT02865135
Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer
A Phase 1/2 study testing DPX-E7 vaccine and Cyclophosphamide in people with Cancer of Head and Neck and Cancer of Cervix, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is studying a therapeutic vaccine, named DPX-E7, as a possible treatment for Human Papilloma Virus or HPV related head and neck, cervical or anal cancer (positive for HLA-A*02). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Head and Neck, Cancer of Cervix, Cancer of Anus
- What is being tested?
- DPX-E7 vaccine and Cyclophosphamide
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2017to 6 Feb 2023
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must be positive for HLA-A*02 and meet all of the following inclusion criteria to be enrolled in the study:
- Histologically or cytologically proven HPVOC or cervical cancer or anal cancer, based on expression of HPV type16 in immunohistochemistry and/or HPV 16 DNA analysis by ISH of tumor tissue from the primary or metastatic lesions.
- Incurable HPVOC, as defined by:
- Relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment (e.g. Surgery, radiotherapy or chemoradiotherapy) with no potentially curative option (i.e. surgery or radiation); OR
- Distant metastasis
- Incurable cervical or anal cancer, as defined by:
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- Relapsed or progressive disease at the primary site and/or regional lymph nodes after initial treatment (e.g. systemic chemotherapy) with no potentially curative option (i.e. surgery or chemoradiotherapy). Chemotherapy administered in conjunction with primary radiation as a radiosensitizer will not be counted as a systemic chemotherapy regimen; OR
- Distant metastasis refractory to initial treatment (at least one prior chemotherapeutic regimen which can include a single chemotherapeutic, a combination of chemotherapeutics, or biologic drugs such as bevacizumab).
- Accessible tumors for sequential biopsies Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.03) to grade 1 or better (except for < grade 2 neuropathy, alopecia, xerostomia, dysphagia, or mucositis);
- Age ≥ 18 years;
- Measurable disease, according to modified RECIST 1.1 and irRECIST (Appendix B \& C);
- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 (Appendix A)
- Adequate bone marrow, liver and renal function, defined by:
- Hemoglobin ≥ 10 g/dL;
- Absolute neutrophil count (ANC) ≥ 1000/μL;
- Absolute lymphocyte count ≥ 400/μL;
- Platelet count ≥ 100,000/μL;
- ALT and AST ≤ 2.5 X upper limit of normal (ULN);
- Total bilirubin ≤ 1.5 X ULN; and
- Serum creatinine ≤ 1.5 X ULN;
- Women of child-bearing potential (WOCBP) must be willing to use acceptable means of birth control;
- Men who could potentially father a child must also use birth control
- Signed informed consent
Who cannot join
- Radiotherapy for primary HPVOC within 8 weeks, or radiotherapy for any other reason within 3 weeks prior to the first dose of trial treatment;
- Chemotherapy within 3 weeks prior to the first dose of trial treatment;Other cancer in the past 5 years, except for carcinoma in situ of the cervix or bladder, or non-melanomatous skin cancer;
- Inaccessible tumor or lack of consent for sequential biopsies
- Uncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are radiographically unstable, symptomatic and/or requiring escalating doses of corticosteroids);
- Active hepatitis, known HIV, or other condition that requires immunosuppressive therapy, including current use of high dose systemic corticosteroids;
- Autoimmune disease, such as systemic lupus erythematosis or rheumatoid arthritis, that is active and requires current immunosuppressive therapy;
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- Active uncontrolled serious infection;
- WOCBP who have a positive β-hCG test or are breastfeeding.
- Acute or chronic skin disorders that would interfere with subcutaneous injection of the vaccine or subsequent assessment of potential skin reactions;
- Allergies to any vaccine, that after discussion with Immunovaccine, are serious enough to warrant exclusion from this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase Ib/II Trial To Test The Safety And Efficacy Of Vaccination With HPV16-E711-19 Nanomer For The Treatment Of Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer In HLA-A*02 Positive Patients
This research study is studying a therapeutic vaccine, named DPX-E7, as a possible treatment for Human Papilloma Virus or HPV related head and neck, cervical or anal cancer (positive for HLA-A*02).
Read the detailed description
This is a phase Ib/II clinical trial. DPX-E7 is a therapeutic vaccine, intended to treat HPV-related head and neck, cervical or anal cancer. DPX-E7 is an investigational vaccine and the FDA (the U.S. Food and Drug Administration) has not approved DPX-E7 vaccine as a treatment for any disease.
DPX-E7 is being tested in humans for the first time. DPX-E7 is a kind of immunotherapy that will make the immune system to elicit an anti-tumor response by generating CD8+ T-cells. CD8+ T-cells play a very important role in fighting against viral infections
- Conditions
- Cancer of Head and Neck, Cancer of Cervix, Cancer of Anus
- Being tested
- DPX-E7 vaccine, Cyclophosphamide
- Keywords
- HPV Related Head and Neck, Cervical, Anal Cancer
- Medical subject headings
- Head and Neck Neoplasms, Uterine Cervical Neoplasms, Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DPX-E7 vaccineDrug
Also called HPV vaccine
Therapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer. Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation.
| Study group | Role | What they receive |
|---|---|---|
| DPX-E7 + Cyclophosphamide [Phase Ib Cohort] | Experimental | Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression. Receives: Drug: DPX-E7 vaccine; Drug: Cyclophosphamide |
| DPX-E7 + Cyclophosphamide [Phase II Cohort 1] | Experimental | Participants were enrolled before amendment 10. Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression. Receives: Drug: DPX-E7 vaccine; Drug: Cyclophosphamide |
| DPX-E7 [Phase II Cohort 2] | Experimental | Participants were enrolled after amendment 10. Participants received two 0.50 mL priming doses of DPX-E7 3 weeks apart, followed by 0.2 mL booster dose every 8 weeks until clinical progression. Receives: Drug: DPX-E7 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]
A DLT was defined as any grade 3 or greater adverse event at least possibly related to the study agent including injection site reactions; or grade 2 or greater allergic reactions which occur in a subject prior to day 50, will trigger DLT. In addition, to be considered as DLT, the adverse event must be considered at least possibly related to study treatment. Grade 3 or greater abnormal lab values lasting <= 72 hours might be excluded as DLTs if there are no accompanying clinical signs and symptoms per investigator's discretion.
Measured: Patients were followed for 50 days.
Grade 1-2 Treatment-Related AE Rate
The proportion of participants who experienced grade 1-2 treatment-related adverse events based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms.
Measured: The median follow up was 2.92 months (range 1.25 - 5.88months).
Changes in CD8+ T Cells in Peripheral Blood and Tumor Tissue
'Responders' will be defined as patients with at least a two-fold increase in the number of CD 8+ T cells (dextramer, ELISpot or both methods) in the peripheral blood and tissue at the final analysis.
Measured: Patients were followed 22 days.
Secondary outcomes (4)
Best Overall Response
Best Overall Response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started) based on modified RECIST 1.1 and irRECIST. Per irRECIST, CR was defined as disappearance of all lesions in two consecutive observations not less than four weeks apart; PR was defined as greater than or equal to 50% decrease in tumor burden compared with baseline in two observations at least four weeks apart.
Measured: The median follow up was 2.92 months (range 1.25 - 5.88months).
Median Overall Survival
Overall survival based on the Kaplan-Meier method is defined as the time the start of treatment to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Measured: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Median Progression-Free Survival
PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study or the appearance of one or more new lesions. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Measured: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Time to Progression (TTP)
TTP is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Participants alive without PD were censored at the earliest of the date of the last disease evaluation. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study or the appearance of one or more new lesions. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Measured: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study start30 Mar 2017
- Primary completion4 Oct 2019
- Study completion6 Feb 2023
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.
- Other trials for Cancer of Head and NeckStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Stand Up To Cancer
- Responsible party
- Principal investigator, Kartik Sehgal, MD, Dana-Farber Cancer Institute
- Investigators
- Kartik Seghal, MD, Principal investigator, Dana-Farber Cancer Institute, Boston, MA02215
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02865135
- Sponsor's protocol ID
- 15-578
- Status last verified
- Jan 2024
- First submitted
- 14 Jul 2016
- Last updated
- 11 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Trial To Test The Safety And Efficacy Of Vaccination With HPV16-E711-19 Nanomer For The Treatment Of Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer In HLA-A*02 Positive Patients
- ClinicalTrials.gov ID
- NCT02865135
- Acronym / sponsor ID
- 15-578
- Conditions
- Cancer of Head and Neck, Cancer of Cervix, Cancer of Anus
- Keywords
- HPV Related Head and Neck, Cervical, Anal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Stand Up To Cancer
- Study start
- 30 Mar 2017 (actual)
- Primary completion
- 4 Oct 2019 (actual)
- Study completion
- 6 Feb 2023 (actual)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Posted 11 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a therapeutic vaccine, named DPX-E7, as a possible treatment for Human Papilloma Virus or HPV related head and neck, cervical or anal cancer (positive for HLA-A*02).
Detailed description
This is a phase Ib/II clinical trial. DPX-E7 is a therapeutic vaccine, intended to treat HPV-related head and neck, cervical or anal cancer. DPX-E7 is an investigational vaccine and the FDA (the U.S. Food and Drug Administration) has not approved DPX-E7 vaccine as a treatment for any disease.
DPX-E7 is being tested in humans for the first time. DPX-E7 is a kind of immunotherapy that will make the immune system to elicit an anti-tumor response by generating CD8+ T-cells. CD8+ T-cells play a very important role in fighting against viral infections
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DPX-E7 + Cyclophosphamide [Phase Ib Cohort] | Experimental | Drug: DPX-E7 vaccine, Drug: CyclophosphamideParticipants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression. |
| DPX-E7 + Cyclophosphamide [Phase II Cohort 1] | Experimental | Drug: DPX-E7 vaccine, Drug: CyclophosphamideParticipants were enrolled before amendment 10. Participants received: 1) 50 mg twice per day of cyclophosphamide orally 7 days before the vaccination, continuing for 7 days on and then 7 days off, throughout the treatment period; 2) two 0.25 mL priming doses of DPX-E7 3 weeks apart, followed by 0.1 mL booster dose every 8 weeks until clinical progression. |
| DPX-E7 [Phase II Cohort 2] | Experimental | Drug: DPX-E7 vaccineParticipants were enrolled after amendment 10. Participants received two 0.50 mL priming doses of DPX-E7 3 weeks apart, followed by 0.2 mL booster dose every 8 weeks until clinical progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Each patient must be positive for HLA-A*02 and meet all of the following inclusion criteria to be enrolled in the study:
- Histologically or cytologically proven HPVOC or cervical cancer or anal cancer, based on expression of HPV type16 in immunohistochemistry and/or HPV 16 DNA analysis by ISH of tumor tissue from the primary or metastatic lesions.
- Incurable HPVOC, as defined by:
- Incurable cervical or anal cancer, as defined by:
- Accessible tumors for sequential biopsies Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.03) to grade 1 or better (except for < grade 2 neuropathy, alopecia, xerostomia, dysphagia, or mucositis);
Key exclusion criteria (10 listed)
- Radiotherapy for primary HPVOC within 8 weeks, or radiotherapy for any other reason within 3 weeks prior to the first dose of trial treatment;
- Chemotherapy within 3 weeks prior to the first dose of trial treatment;Other cancer in the past 5 years, except for carcinoma in situ of the cervix or bladder, or non-melanomatous skin cancer;
- Inaccessible tumor or lack of consent for sequential biopsies
- Uncontrolled central nervous system (CNS) metastases (i.e. known CNS lesions that are radiographically unstable, symptomatic and/or requiring escalating doses of corticosteroids);
- Active hepatitis, known HIV, or other condition that requires immunosuppressive therapy, including current use of high dose systemic corticosteroids;
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 |
|---|---|---|
| DPX-E7 vaccineAlso: HPV vaccineTherapeutic vaccine for the treatment of incurable HPV16-related oropharyngeal, cervical and anal cancer in HLA-A*02 positive patients. | Drug | DPX-E7 + Cyclophosphamide [Phase II Cohort 1], DPX-E7 + Cyclophosphamide [Phase Ib Cohort], DPX-E7 [Phase II Cohort 2] |
| CyclophosphamideAlso: CytoxanCyclophosphamide is a medication primarily used in the management and treatment of neoplasms, including multiple myeloma, sarcoma, and breast cancer. Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation. | Drug | DPX-E7 + Cyclophosphamide [Phase II Cohort 1], DPX-E7 + Cyclophosphamide [Phase Ib Cohort] |
Primary outcome
Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b]
Time frame: Patients were followed for 50 days.
A DLT was defined as any grade 3 or greater adverse event at least possibly related to the study agent including injection site reactions; or grade 2 or greater allergic reactions which occur in a subject prior to day 50, will trigger DLT. In addition, to be considered as DLT, the adverse event must be considered at least possibly related to study treatment. Grade 3 or greater abnormal lab values lasting <= 72 hours might be excluded as DLTs if there are no accompanying clinical signs and symptoms per investigator's discretion.
Grade 1-2 Treatment-Related AE Rate
Time frame: The median follow up was 2.92 months (range 1.25 - 5.88months).
The proportion of participants who experienced grade 1-2 treatment-related adverse events based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms.
Changes in CD8+ T Cells in Peripheral Blood and Tumor Tissue
Time frame: Patients were followed 22 days.
'Responders' will be defined as patients with at least a two-fold increase in the number of CD 8+ T cells (dextramer, ELISpot or both methods) in the peripheral blood and tissue at the final analysis.
4 secondary outcomes
Best Overall Response
Time frame: The median follow up was 2.92 months (range 1.25 - 5.88months).
Median Overall Survival
Time frame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Median Progression-Free Survival
Time frame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Time to Progression (TTP)
Time frame: The median follow up was 4.8 months (range 1.6 - 14.9 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Kartik Seghal, MD principal investigator
Dana-Farber Cancer Institute, Boston, MA02215
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DPX-E7 vaccine and Cyclophosphamide in people with Cancer of Head and Neck and Cancer of Cervix, run by Dana-Farber Cancer Institute 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 23 inclusion and 10 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 11 Jan 2024. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Jan 2024). 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 Dose Limiting Toxicity (DLT) [Phase 1b] (time frame: Patients were followed for 50 days.). The study lists 3 primary outcomes in all. 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 11 Jan 2024.