Cervical AdenocarcinomaPhase 2BROTHERNCT06805864
Pembrolizumab Concurrent With and Following Carbon-ion Radiotherapy for Locally Advanced Cervical Adenocarcinoma
A Phase 2 study testing Pembrolizumab (KEYTRUDA®) in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by Gunma University at 1 site in Japan.
Trial summary
The goal of this clinical trial is to learn if pembrolizumab works for cervical adenocarcinoma treat with concurrent chemo-carbon-ion radiaotherapy (CIRT). The main questions it aims to answer are: Does concurrent chemo-CIRT with pembrolizumab improves 2-year progression-free survival (PFS), compared with concurrent… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma
- What is being tested?
- Pembrolizumab (KEYTRUDA®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteJapan
- Study dates
- 1 Feb 2025to 31 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- 1. Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed adenocarcinoma or adenosquamous carcinoma of the uterine cervix and Stage ⅡA2, ⅡB, ⅢA, ⅢB, ⅢC1r, IVA according to FIGO classification (2018) will be enrolled in this study.
- 2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- 3. Have measurable disease based on RECIST 1.1.
- 4. Archival tumor tissue sample or a newly obtained biopsy of a tumor lesion that was not previously irradiated was provided. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsy samples are preferred to archived tissues.
- 5. 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 first dose of pembrolizumab.
- 6. Have adequate organ function below. Specimens must be collected within 10 days to the start of pembrolizumab administration.
- Absolute neutrophil count (ANC) ≥ 1500/µL, Platelets ≥ 100000/µ, Hemoglobin ≥9.0 g/dL or ≥ 5.6 mmol/L, Creatinine clearance ≥ 50 mL/min, Total bilirubin ≤1.5 ×ULN or direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN, AST and ALT ≤2.5 × ULN, International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
Who cannot join
- 1. 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 (e.g., CTLA-4, OX-40, CD137).
- 2. Has received prior radical surgery, RT, or systemic therapy (including investigational drugs) for cervical cancer. Note: Conization for localized cervical tumors is allowed.
- 3. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
- Note: please refer to Section 5.3 for information on COVID-19 vaccines
- 4. Has received an investigational agent or has used an investigational device within 4 weeks prior to pembrolizumab administration.
- 5. 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 pembrolizumab.
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- 6. 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, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
- 7. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
- 8. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid).
- 9. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- 10. Has an active infection requiring systemic therapy.
- 11. History of active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection.
- 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 14. Is pregnant or breast feeding, 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.
- 15. Has had an allogenic tissue/solid organ transplant.
- 16. History of HIV infection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Japan1 site
Gunma University Hospital
Maebashi, Gunma, 371-8511
Tatsuya Ohno, M.D., Ph.D., +81-27-220-8383, tohno@gunma-u.ac.jp
About this study
Official title: Pembrolizumab Concurrent With and Following Carbon-ion Radiotherapy for Locally Advanced Cervical Adenocarcinoma (BROTHER STUDY)
The goal of this clinical trial is to learn if pembrolizumab works for cervical adenocarcinoma treat with concurrent chemo-carbon-ion radiaotherapy (CIRT).
The main questions it aims to answer are:
- Does concurrent chemo-CIRT with pembrolizumab improves 2-year progression-free survival (PFS), compared with concurrent chemoradiotherapy with conventional X-rays?
- Being tested
- Pembrolizumab (KEYTRUDA®)
- Keywords
- Cervical Cancer, Carbon-ion Radiotherapy, Pembrolizumab
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab (KEYTRUDA®)Drug
Pembrolizumab is administered at 200 mg every 3 weeks for the first 2 cycles during Chemo-CIRT, after completion of radiotherapy, the dose is increased to 400 mg and given every 6 weeks for a total of 17 cycles over 2 years.
| Study group | Role | What they receive |
|---|---|---|
| CIRT＋CDDP＋Pembro | Experimental | Patients will first be treated with 16 fractions/4 weeks of carbon-ion radiation therapy (CIRT) followed by 3 cycles/2 weeks of image-guided brachytherapy (IGBT). During this radiation therapy, up to 5 cycles of weekly cisplatin will be given concurrently.
In addition to these, pembrolizumab will be administered every 3 weeks at 200 mg for the first 2 cycles, then increased to 400 mg every 6 weeks for 17 cycles over 2 years. Receives: Drug: Pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
It is based on the investigator's RECIST 1.1 assessment, or in the absence of imaging evidence of disease progression based on RECIST 1.1, histologically confirmed PD, after concurrent chemo-CIRT with pembrolizumab.
Measured: At 2 years after the start of trial treatment
Secondary outcomes (4)
Overall survival (OS)
To evaluate the 2-year overall survival after concurrent chemo-CIRT with pembrolizumab.
Measured: At 2 years after the start of trial treatment
Complete response (CR) rate
To evaluate the complete response (CR) rate, defined as the maximum response of the primary tumor based on RECIST 1.1 assessment at 6 months after initiation of CIRT.
Measured: At 6 months after the start of trial treatment
Local control (LC)
To evaluate the 2-year local control (LC) after concurrent chemo-CIRT with pembrolizumab.
Measured: At 2 years after the start of trial treatment
Acute and late toxicities
To evaluate the acute and late toxicities of concurrent chemo-CIRT with pembrolizumab.
Measured: Acute (≤ 90 days) and late toxicities (> 90 days) over 2 years after the start of trial treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2025
- Study start1 Feb 2025 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical AdenocarcinomaStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gunma University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Tatsuya Ohno, Gunma University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06805864
- Sponsor's protocol ID
- IRB2024-049
- Acronym
- BROTHER
- Status last verified
- Jan 2025
- First submitted
- 28 Jan 2025
- Last updated
- 3 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab Concurrent With and Following Carbon-ion Radiotherapy for Locally Advanced Cervical Adenocarcinoma (BROTHER STUDY)
- ClinicalTrials.gov ID
- NCT06805864
- Acronym / sponsor ID
- BROTHER / IRB2024-049
- Keywords
- Cervical Cancer, Carbon-ion Radiotherapy, Pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Gunma UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Feb 2025 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 3 Feb 2025 (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.
The goal of this clinical trial is to learn if pembrolizumab works for cervical adenocarcinoma treat with concurrent chemo-carbon-ion radiaotherapy (CIRT).
The main questions it aims to answer are:
- Does concurrent chemo-CIRT with pembrolizumab improves 2-year progression-free survival (PFS), compared with concurrent chemoradiotherapy with conventional X-rays?
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CIRT＋CDDP＋Pembro | Experimental | Drug: Pembrolizumab (KEYTRUDA®)Patients will first be treated with 16 fractions/4 weeks of carbon-ion radiation therapy (CIRT) followed by 3 cycles/2 weeks of image-guided brachytherapy (IGBT). During this radiation therapy, up to 5 cycles of weekly cisplatin will be given concurrently. In addition to these, pembrolizumab will be administered every 3 weeks at 200 mg for the first 2 cycles, then increased to 400 mg every 6 weeks for 17 cycles over 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed adenocarcinoma or adenosquamous carcinoma of the uterine cervix and Stage ⅡA2, ⅡB, ⅢA, ⅢB, ⅢC1r, IVA according to FIGO classification (2018) will be enrolled in this study.
- 2. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- 3. Have measurable disease based on RECIST 1.1.
- 4. Archival tumor tissue sample or a newly obtained biopsy of a tumor lesion that was not previously irradiated was provided. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsy samples are preferred to archived tissues.
- 5. 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 first dose of pembrolizumab.
Key exclusion criteria (18 listed)
- 1. 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 (e.g., CTLA-4, OX-40, CD137).
- 2. Has received prior radical surgery, RT, or systemic therapy (including investigational drugs) for cervical cancer. Note: Conization for localized cervical tumors is allowed.
- 3. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
- Note: please refer to Section 5.3 for information on COVID-19 vaccines
- 4. Has received an investigational agent or has used an investigational device within 4 weeks prior to pembrolizumab administration.
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 |
|---|---|---|
| Pembrolizumab (KEYTRUDA®)Pembrolizumab is administered at 200 mg every 3 weeks for the first 2 cycles during Chemo-CIRT, after completion of radiotherapy, the dose is increased to 400 mg and given every 6 weeks for a total of 17 cycles over 2 years. | Drug | CIRT＋CDDP＋Pembro |
Primary outcome
Progression-free survival (PFS)
Time frame: At 2 years after the start of trial treatment
It is based on the investigator's RECIST 1.1 assessment, or in the absence of imaging evidence of disease progression based on RECIST 1.1, histologically confirmed PD, after concurrent chemo-CIRT with pembrolizumab.
4 secondary outcomes
Overall survival (OS)
Time frame: At 2 years after the start of trial treatment
Complete response (CR) rate
Time frame: At 6 months after the start of trial treatment
Local control (LC)
Time frame: At 2 years after the start of trial treatment
Acute and late toxicities
Time frame: Acute (≤ 90 days) and late toxicities (> 90 days) over 2 years after the start of trial treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- 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.
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 (KEYTRUDA®) in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by Gunma University at 1 site in Japan.
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 7 inclusion and 18 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: opening soon, as of the sponsor's last update on 3 Feb 2025. 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 Japan. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tatsuya Ohno, M.D., Ph.D. (+81-27-220-8383, tohno@gunma-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: At 2 years after the start of trial treatment). 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 3 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.