Cervical, Vaginal and Vulval Inflammatory DiseasesPhase 2MITO CERV 4NCT04211103
Pembrolizumab in Pre Neoplastic High Grade HPV-related Vulvar and Cervical Lesions
A Phase 2 study testing Pembrolizumab in people with Cervical, Vaginal and Vulval Inflammatory Diseases, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 9 sites in Italy.
Trial summary
single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical, Vaginal and Vulval Inflammatory Diseases
- What is being tested?
- Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 9 sitesItaly
- Study dates
- 14 Oct 2020to 1 Sep 2024
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cervical HSIL OR vulvar VIN 2-3 lesions will be enrolled in this study.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of study treatment.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have provided archival tumor tissue sample (if pre treatment biopsy performed at other institution) or newly obtained core or excisional biopsy of the lesion. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
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- Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of registration .
- Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to [randomization /allocation].
- Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
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- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma) that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as qualitative HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Italy9 sites, 9 recruiting
- Recruiting
Centro di Riferimento Oncologico
Aviano
- Recruiting
Policlinico S.Orsola-Malpighi
Bologna
- Recruiting
Ospedale "degli Infermi"
Faenza
- Recruiting
Ospedale "Umberto I"
Lugo
- Recruiting
Ospedale Sacro Cuore Don Calabria
Negrar
- Recruiting
Ospedale Santa Maria delle Croci
Ravenna
- Recruiting
Ospedale Infermi
Rimini
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
- Recruiting
Istituti fisioterapici Ospitalieri - Istituto Tumori Regina Elena
Rome
About this study
Official title: Single Arm Phase II Study on Pembrolizumab in Pre Neoplastic High Grade HPV-related Vulvar and Cervical Lesions
single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions.
Read the detailed description
This is a single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions. Patients with histologically confirmed H-SIL and/or VIN 2-3 lesions will be treated with Pembrolizumab 200 mg flat dose every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy.
- Being tested
- Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Humanized antibody used in cancer immunotherapy. It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab single agent | Experimental | Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy.
Pembrolizumab 200 mg flat dose will be administered every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of Pembrolizumab: proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment
proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment
Measured: 18 months
Secondary outcomes (5)
Efficacy of Pembrolizumab: Proportion of subjects with no evidence of vulvar VIN 2-3 on histology at surgical treatment
Proportion of subjects with no evidence of vulvar VIN 2-3 on histology at surgical treatment
Measured: 18 months
Efficacy of Pembrolizumab: Incidence and severity of systemic events for the duration of the study (CTCAE 5.0)
Incidence and severity of systemic events for the duration of the study (CTCAE 5.0)
Measured: 18 months
Efficacy of Pembrolizumab: Proportion of subjects with downstaging of cervical and vulvar pre-neoplastic lesion on histology
Proportion of subjects with downstaging of cervical and vulvar pre-neoplastic lesion on histology
Measured: 18 months
Efficacy of Pembrolizumab: Proportion of patients with no evidence of HPV by HPV testing at Week 36 visit
Proportion of patients with no evidence of HPV by HPV testing at Week 36 visit
Measured: 18 months
Efficacy of Pembrolizumab: Proportion of subjects with no progression of cervical HSIL and vulvar VIN 2-3 to cervical and vulvar carcinoma respectively from baseline on histology
Proportion of subjects with no progression of cervical HSIL and vulvar VIN 2-3 to cervical and vulvar carcinoma respectively from baseline on histology
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2019
- Study start14 Oct 2020
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical, Vaginal and Vulval Inflammatory DiseasesStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single arm phase II trial
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04211103
- Sponsor's protocol ID
- 2773
- Acronym
- MITO CERV 4
- Status last verified
- Aug 2021
- First submitted
- 22 Dec 2019
- Last updated
- 27 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase II Study on Pembrolizumab in Pre Neoplastic High Grade HPV-related Vulvar and Cervical Lesions
- ClinicalTrials.gov ID
- NCT04211103
- Acronym / sponsor ID
- MITO CERV 4 / 2773
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 14 Oct 2020 (actual)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 26 Dec 2019 (actual)
- 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.
single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions.
Detailed description
This is a single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions. Patients with histologically confirmed H-SIL and/or VIN 2-3 lesions will be treated with Pembrolizumab 200 mg flat dose every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single arm phase II trial
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab single agent | Experimental | Drug: PembrolizumabPembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy. Pembrolizumab 200 mg flat dose will be administered every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cervical HSIL OR vulvar VIN 2-3 lesions will be enrolled in this study.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have provided archival tumor tissue sample (if pre treatment biopsy performed at other institution) or newly obtained core or excisional biopsy of the lesion. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
Key exclusion criteria (23 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to [randomization /allocation].
- Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
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 |
|---|---|---|
| PembrolizumabAlso: KeytrudaHumanized antibody used in cancer immunotherapy. It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. | Drug | Pembrolizumab single agent |
Primary outcome
Efficacy of Pembrolizumab: proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment
Time frame: 18 months
proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment
5 secondary outcomes
Efficacy of Pembrolizumab: Proportion of subjects with no evidence of vulvar VIN 2-3 on histology at surgical treatment
Time frame: 18 months
Efficacy of Pembrolizumab: Incidence and severity of systemic events for the duration of the study (CTCAE 5.0)
Time frame: 18 months
Efficacy of Pembrolizumab: Proportion of subjects with downstaging of cervical and vulvar pre-neoplastic lesion on histology
Time frame: 18 months
Efficacy of Pembrolizumab: Proportion of patients with no evidence of HPV by HPV testing at Week 36 visit
Time frame: 18 months
Efficacy of Pembrolizumab: Proportion of subjects with no progression of cervical HSIL and vulvar VIN 2-3 to cervical and vulvar carcinoma respectively from baseline on histology
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2021.
- Individual participant dataSharing planned: No
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.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Cervical, Vaginal and Vulval Inflammatory Diseases, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 9 sites in Italy.
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 9 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 27 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Domenica Lorusso, MD (0630157337 ext. 0039, domenica.lorusso@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Pembrolizumab: proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment (time frame: 18 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 27 Aug 2021.