Cervical CancerPhase 1/2NCT04651127
Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer
A Phase 1/2 study testing Toripalimab + Chidamide in people with Cervical Cancer and Cervix Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Cervical Cancer, Cervix Cancer, Cervix Neoplasm
- What is being tested?
- Toripalimab + Chidamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 9 Nov 2020to 26 Jan 2023
- Phase
- Phase 1/2
- 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 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form (ICF).
- Patients must have histologically confirmed diagnosis of metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
- Age ≥ 18 years and ≤ 70 years.
- Patients must have measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy exceeds 3 months.
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- Patients must have progressed on at least one line of platinum-based systemic therapy.
- Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic cervical cancer. However, adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 6 months of completion of therapy.
- Patients must have adequate organ function as defined by the following criteria:
- Absolute neutrophil count (ANC) (≥ 1.5×10^9/L), hemoglobin of ≥ 90 g/L, platelets ≥ 80 ×10^9/L
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
- Baseline albumin ≥ 28 g/L
- Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤ 1 × ULN may be enrolled)
Who cannot join
- Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to HDAC inhibitors.
- Any condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before first dose of study drug. Corticosteroids for topical use, nasal spray, and inhaled steroids are allowed.
- Active autoimmune diseases that require systemic treatment. Alternative treatments (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted.
- Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association [NYHA] class > 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
- Arterial or venous thrombosis within 6 months before enrollment
- Uncontrolled hypertension defined as systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg despite antihypertensive drugs.
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- Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
- Coagulation abnormalities (INR > 2.0, PT > 16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- Has known active central nervous system metastases.
- Patients had a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has a known history of immunodeficiency including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
- Has known active Hepatitis B or Hepatitis C.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Toripalimab, a Anti-PD-1 Antibody, and Histone Deacetylase Inhibitor Chidamide in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer, a Multicenter, Open-label, Single-arm, Phase Ib/II Trial
Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. Pembrolizumab has been approved for second-line treatment in patients with advanced PD-L1-positive cervical cancer. However, the response rate achieved by PD-1 inhibitors as monotherapy is only modest. Preclinical studies found that in mouse models of B-cell lymphoma, adding a histone deacetylase (HDAC) inhibitor sensitized cancers to anti-PD-1 therapy. Recently, combination treatment of HDAC inhibitors with immune checkpoint inhibitors is widely investigated and has promising results in several cancer types. Toripalimab is a humanized IgG4 monoclonal antibody against PD-1. Chidamide is a class I HDAC inhibitor. Here we conducted a phase Ib/II, single-arm, multi-center study to evaluate the efficacy and safety of toripalimab in combination with chidamide in patients with metastatic, persistent, or recurrent cervical cancer.
Read the detailed description
There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if RP2D reached in Part A, or not initiated if RP2D was not reached in Part A. Part A has been designed to identify the recommended dose of combination of toripalimab plus chidamide for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 28 days. "3+3"design was used in the dose finding cohort. If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week) till disease progression (PD) withdraw of consent, or unacceptable toxicity.
- Conditions
- Cervical Cancer, Cervix Cancer, Cervix Neoplasm
- Being tested
- Toripalimab + Chidamide
- 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.
Toripalimab + ChidamideDrug
In combination dose finding phase, phase 1b will begin with Dose Level 1: chidamide 30 mg/day orally (twice a week) and toripalimab (240mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (chidamide 25 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously) and Dose Level 3 (chidamide 20 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously). If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week).
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab + Chidamide Arm | Experimental | Not described Receives: Drug: Toripalimab + Chidamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of the combination of toripalimab and chidamide (Phase Ib)
Dose-limiting toxicities (DLTs) are defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and grade 3 non-hematologic toxicities according to CTCAE v5.0
Measured: first 28 days of treatment
Objective Response Rate (ORR) (Phase II)
ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: from the first drug administration up to two years
Secondary outcomes (5)
Progression-free Survival (PFS)
Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first.
Measured: from the first drug administration up to two years
Duration of response (DOR)
Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
Measured: from the first drug administration up to two years
Disease Control Rate (DCR)
Proportion of patients whose best overall response is either CR, PR, or SD according to RECIST v1.1.
Measured: from the first drug administration up to two years
Overall survival (OS)
Time from the date of first study treatment administration to the date of death due to any cause.
Measured: from the first drug administration up to two years
Safety and tolerability
Incidence of Adverse Event reported per CTCAE v5.0
Measured: up to 90 days after last study treatment administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2020
- Study start9 Nov 2020
- Primary completion26 Jan 2023
- Study completion26 Jan 2023
Why it stopped: Five patients were enrolled in the study, but no treatment response was observed and all the patients had the best of response of prgressive disease. Given the lack of efficacy, the trial was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xin Huang, Sun Yat-sen University
- Investigators
- Xin Huang, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04651127
- Sponsor's protocol ID
- B2020-229-01
- Status last verified
- Mar 2026
- First submitted
- 25 Nov 2020
- Last updated
- 10 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toripalimab, a Anti-PD-1 Antibody, and Histone Deacetylase Inhibitor Chidamide in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer, a Multicenter, Open-label, Single-arm, Phase Ib/II Trial
- ClinicalTrials.gov ID
- NCT04651127
- Acronym / sponsor ID
- B2020-229-01
- Conditions
- Cervical Cancer, Cervix Cancer, Cervix Neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Five patients were enrolled in the study, but no treatment response was observed and all the patients had the best of response of prgressive disease. Given the lack of efficacy, the trial was terminated.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 26 Jan 2023 (actual)
- Study completion
- 26 Jan 2023 (actual)
- First posted
- 3 Dec 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.
Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. Pembrolizumab has been approved for second-line treatment in patients with advanced PD-L1-positive cervical cancer. However, the response rate achieved by PD-1 inhibitors as monotherapy is only modest. Preclinical studies found that in mouse models of B-cell lymphoma, adding a histone deacetylase (HDAC) inhibitor sensitized cancers to anti-PD-1 therapy. Recently, combination treatment of HDAC inhibitors with immune checkpoint inhibitors is widely investigated and has promising results in several cancer types. Toripalimab is a humanized IgG4 monoclonal antibody against PD-1. Chidamide is a class I HDAC inhibitor. Here we conducted a phase Ib/II, single-arm, multi-center study to evaluate the efficacy and safety of toripalimab in combination with chidamide in patients with metastatic, persistent, or recurrent cervical cancer.
Detailed description
There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if RP2D reached in Part A, or not initiated if RP2D was not reached in Part A. Part A has been designed to identify the recommended dose of combination of toripalimab plus chidamide for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 28 days. "3+3"design was used in the dose finding cohort. If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week) till disease progression (PD) withdraw of consent, or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab + Chidamide Arm | Experimental | Drug: Toripalimab + Chidamide |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed Informed Consent Form (ICF).
- Patients must have histologically confirmed diagnosis of metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
- Age ≥ 18 years and ≤ 70 years.
- Patients must have measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (12 listed)
- Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to HDAC inhibitors.
- Any condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before first dose of study drug. Corticosteroids for topical use, nasal spray, and inhaled steroids are allowed.
- Active autoimmune diseases that require systemic treatment. Alternative treatments (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted.
- Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association [NYHA] class > 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
- Arterial or venous thrombosis within 6 months before enrollment
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 |
|---|---|---|
| Toripalimab + ChidamideIn combination dose finding phase, phase 1b will begin with Dose Level 1: chidamide 30 mg/day orally (twice a week) and toripalimab (240mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (chidamide 25 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously) and Dose Level 3 (chidamide 20 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously). If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week). | Drug | Toripalimab + Chidamide Arm |
Primary outcome
To evaluate the safety and tolerability of the combination of toripalimab and chidamide (Phase Ib)
Time frame: first 28 days of treatment
Dose-limiting toxicities (DLTs) are defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and grade 3 non-hematologic toxicities according to CTCAE v5.0
Objective Response Rate (ORR) (Phase II)
Time frame: from the first drug administration up to two years
ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5 secondary outcomes
Progression-free Survival (PFS)
Time frame: from the first drug administration up to two years
Duration of response (DOR)
Time frame: from the first drug administration up to two years
Disease Control Rate (DCR)
Time frame: from the first drug administration up to two years
Overall survival (OS)
Time frame: from the first drug administration up to two years
Safety and tolerability
Time frame: up to 90 days after last study treatment administration
Results and safety
The study was stopped early (reason given: Five patients were enrolled in the study, but no treatment response was observed and all the patients had the best of response of prgressive disease. Given the lack of efficacy, the trial was terminated.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
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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.
Xin Huang principal investigator
Sun Yat-Sen University Cancer Center
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 Toripalimab + Chidamide in people with Cervical Cancer and Cervix Cancer, run by Sun Yat-sen University at 1 site in China.
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 15 inclusion and 12 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: stopped early, as of the sponsor's last update on 10 Mar 2026. 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 China. 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?
The study was stopped early (reason given: Five patients were enrolled in the study, but no treatment response was observed and all the patients had the best of response of prgressive disease. Given the lack of efficacy, the trial was terminated.). Results are not available in the source record.
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?
To evaluate the safety and tolerability of the combination of toripalimab and chidamide (Phase Ib) (time frame: first 28 days of treatment). The study lists 2 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 10 Mar 2026.