Locally Advanced Cervical CancerPhase 2MITO CERV 3NCT04238988
Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
A Phase 2 study testing Pembrolizumab, Carboplatin and Taxol in people with Locally Advanced Cervical Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Single arm multicenter phase II trial evaluating the role of Pembrolizumab in combination to Carboplatin-Paclitaxel chemotherapy in locally advanced cervical cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Locally Advanced Cervical Cancer
- What is being tested?
- Pembrolizumab, Carboplatin and Taxol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteItaly
- Study dates
- 18 Feb 2021to 1 Sep 2023
- 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 FIGO Stage IB2-IIB cervical cancer will be enrolled in this study. Squamous, adenocarcinoma and adenosquamous histotypes are admitted.
- PDL1+>1% of cell by IHC evaluation in tumor cells
- Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 4 months after the end of treatment
Show all 13Show fewer
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor 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.
- 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 treatment initiation.
- 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.
- No previous systemic chemotherapy or radiation therapy for cervical cancer
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior radiotherapy within 2 weeks of start of study treatment for palliative intent. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- 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.
Show all 27Show fewer
- 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, cervical cancer in situ) 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).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
- 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.
- History of cerebrovascular accident, pulmonary embolism or untreated grade 3 deep venous thrombosis (DVT) within the past 6 months
- NCI CTCAE (version 5.0) grade ≥2 enteritis
- History of myocardial infarction, unstable angina, subarachnoid haemorrhage, stroke or transient ischaemic attack within 6 months before first dose of study drug
- Clinically significant active cardiovascular disease (e.g., New York Heart Association class II or greater congestive heart failure [CHF], aortic aneurysm)
- Serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months before study enrolment
- Pre-existing NCI CTCAE (version 5.0) grade ≥2 peripheral neuropathy
- -
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
About this study
Official title: Phase II Study on Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
Single arm multicenter phase II trial evaluating the role of Pembrolizumab in combination to Carboplatin-Paclitaxel chemotherapy in locally advanced cervical cancer patients.
Read the detailed description
Patients with stage IB2-IIB cervical cancer will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q 21)+ Pembrolizumab (200 mg flat dose every 3 weeks).
After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will undergo radical surgery.
After surgery, patients presenting with high risk factors (positive lymphnodes, positive parametria, positive surgical margins or at least 2 of the following risk factor between tumor diameter >3 cm, LVSI, stromal infiltration >1/3) will receive 3 cycles of adjuvant Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient consent withdrawal for up to 35 cycles.
- Conditions
- Locally Advanced Cervical Cancer
- Being tested
- Pembrolizumab, Carboplatin, Taxol
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.
CarboplatinDrug
Chemotherapy medication
TaxolDrug
Also called Paclitaxel
Chemotherapy medication
| Study group | Role | What they receive |
|---|---|---|
| Carboplatin-Paclitaxel-Pembrolizumab | Experimental | Patients will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q 21)+ Pembrolizumab (200 mg flat dose every 3 weeks).
After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will undergo radical surgery.
After surgery, patients presenting with high risk factors will receive 3 cycles of adjuvant Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient consent withdrawal for up to 35 cycles. Receives: Drug: Pembrolizumab; Drug: Carboplatin; Drug: Taxol |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-years Progression-free survival
The combination of Pembrolizumab-chemotherapy is expected to increase 2-years progression free survival with respect to historical controls.
Measured: 42 months
Secondary outcomes (10)
Overall survival
The combination of pembrolizumab- chemotherapy is expected to increase overall survival with respect to historical controls
Measured: 42 months
Clinical Response rate
The combination of pembrolizumab-chemotherapy is expected to increase clinical response rate with respect to historical controls
Measured: 42 months
Pathologic optimal response
The combination of pembrolizumab-chemotherapy is expected to increase pathologic response rate with respect to historical controls
Measured: 42 months
Adverse events
The combination of pembrolizumab-chemotherapy is expected to have an acceptable toxicity profile
Measured: 42 months
Quality of life
At baseline, every 3 cycles during the chemotherapy treatment phase, at chemotherapy completion, 6 months after chemotherapy completion, 1 and 2 years after chemotherapy completion and at progression, will be assessed the quality of life of patients according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and CX24. The questionnaires record in a scale from 1 (better outcome) to 4 (worse outcome) the physical, role, emotional, cognitive and social function of patients.
Measured: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
1)Messenger RNA (mRNA) transcript profiling will be performed.
Measured: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
blood sample will be collected before cycle 1, before cycle 6 and at progression. CD3 cells will be isolated and CD4/CD8 ratio will be evaluated by FACS analyses.
Measured: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
serum levels of IL -2, IL-10; TGF- Beta and IL-6 will be assessed.
Measured: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
tumor biopsies at progression will be collected in order to determine the PD-1R infiltrating lymphocyte population before and after treatment.
Measured: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
single and dual staining IHC analysis of: OX40-OX40L; ICOS; PD1, PD-L1, PD2, PDL2 and CTLA-4; FOXP3 and CD4; CD95 and CD95L
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start18 Feb 2021
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Cervical CancerStudies 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 multicenter 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
- NCT04238988
- Sponsor's protocol ID
- 2586
- Acronym
- MITO CERV 3
- Status last verified
- Aug 2021
- First submitted
- 27 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
- Phase II Study on Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
- ClinicalTrials.gov ID
- NCT04238988
- Acronym / sponsor ID
- MITO CERV 3 / 2586
- Conditions
- Locally Advanced Cervical Cancer
- 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
- 18 Feb 2021 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 23 Jan 2020 (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 multicenter phase II trial evaluating the role of Pembrolizumab in combination to Carboplatin-Paclitaxel chemotherapy in locally advanced cervical cancer patients.
Detailed description
Patients with stage IB2-IIB cervical cancer will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q 21)+ Pembrolizumab (200 mg flat dose every 3 weeks).
After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will undergo radical surgery.
After surgery, patients presenting with high risk factors (positive lymphnodes, positive parametria, positive surgical margins or at least 2 of the following risk factor between tumor diameter >3 cm, LVSI, stromal infiltration >1/3) will receive 3 cycles of adjuvant Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient consent withdrawal for up to 35 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm multicenter phase II trial
| Arm | Type | Receives |
|---|---|---|
| Carboplatin-Paclitaxel-Pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: Carboplatin, Drug: TaxolPatients will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q 21)+ Pembrolizumab (200 mg flat dose every 3 weeks). After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will undergo radical surgery. After surgery, patients presenting with high risk factors will receive 3 cycles of adjuvant Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient consent withdrawal for up to 35 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of FIGO Stage IB2-IIB cervical cancer will be enrolled in this study. Squamous, adenocarcinoma and adenosquamous histotypes are admitted.
- PDL1+>1% of cell by IHC evaluation in tumor cells
- Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), 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.
Key exclusion criteria (27 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior radiotherapy within 2 weeks of start of study treatment for palliative intent. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- 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.
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 | Carboplatin-Paclitaxel-Pembrolizumab |
| CarboplatinChemotherapy medication | Drug | Carboplatin-Paclitaxel-Pembrolizumab |
| TaxolAlso: PaclitaxelChemotherapy medication | Drug | Carboplatin-Paclitaxel-Pembrolizumab |
Primary outcome
2-years Progression-free survival
Time frame: 42 months
The combination of Pembrolizumab-chemotherapy is expected to increase 2-years progression free survival with respect to historical controls.
10 secondary outcomes
Overall survival
Time frame: 42 months
Clinical Response rate
Time frame: 42 months
Pathologic optimal response
Time frame: 42 months
Adverse events
Time frame: 42 months
Quality of life
Time frame: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
Time frame: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
Time frame: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
Time frame: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
Time frame: 42 months
Immune-related gene signatures associated with response or resistance to immune checkpoint blockade
Time frame: 42 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
Related trials for Locally Advanced Cervical Cancer
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 3
Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer
Locally Advanced Cervical Adenocarcinoma, Locally Advanced Cervical Adenosquamous Carcinoma
Not yet recruitingPhase 1/2
Intravenously Administered PROMITIL Combined With Radiotherapy in Patients With Cisplatin-Ineligible Head and Neck Cancer Patients
Head & Neck Squamous Cell Carcinoma, Locally Advanced Head and Neck Squamous Cell Carcinoma
Active, not recruitingPhase 2
Soylent in Reducing Gastrostomy Tube Rates in Patients With Locally Advanced Head and Neck Cancer Undergoing Chemoradiotherapy
Locally Advanced Head and Neck 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.
1 site 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, Carboplatin and Taxol in people with Locally Advanced Cervical Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site 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 13 inclusion and 27 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 1 site 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 Domnica Lorusso, MD (0630157337 ext. +39, domenica.lorusso@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-years Progression-free survival (time frame: 42 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.