Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer
- Conditions
- Cancer of Head and NeckCancer of CervixCancer of Anus
- Interventions
- Drug: DPX-E7 vaccineDrug: Cyclophosphamide
- Registration Number
- NCT02865135
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief 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).
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
-
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.
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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:
- 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);
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Age ≥ 18 years;
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Measurable disease, according to modified RECIST 1.1 and irRECIST (Appendix B & C);
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Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 (Appendix A)
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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;
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Women of child-bearing potential (WOCBP) must be willing to use acceptable means of birth control;
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Men who could potentially father a child must also use birth control
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Signed informed consent
- 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;
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DPX-E7 + Cyclophosphamide [Phase Ib Cohort] DPX-E7 vaccine 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] DPX-E7 vaccine 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. DPX-E7 + Cyclophosphamide [Phase II Cohort 1] DPX-E7 vaccine 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. DPX-E7 + Cyclophosphamide [Phase Ib Cohort] Cyclophosphamide 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 + Cyclophosphamide [Phase II Cohort 1] Cyclophosphamide 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicity (DLT) [Phase 1b] 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 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 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.
- Secondary Outcome Measures
Name Time Method Time to Progression (TTP) The median follow up was 4.8 months (range 1.6 - 14.9 months). 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.
Best Overall Response The median follow up was 2.92 months (range 1.25 - 5.88months). 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.
Median Progression-Free Survival The median follow up was 4.8 months (range 1.6 - 14.9 months). 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.
Median Overall Survival The median follow up was 4.8 months (range 1.6 - 14.9 months). 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.
Trial Locations
- Locations (1)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States