Endometrial CancerPhase 2CAN-RESPONDNCT05550558
Camrelizumab Plus Anlotinib in Patients With Recurrent Sporadic MMRd Endometrial Cancer
A Phase 2 study testing Anlotinib + Camrelizumab in people with Endometrial Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.
Trial summary
Patients with advanced mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) endometrial cancer (EC) are currently treated as one entity, and immune checkpoint inhibitor (ICI) monotherapy is the treatment of choice. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- Anlotinib + Camrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2022to 30 Nov 2027
- 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
- Patients must receive have completed at least 1 but no more than 3 prior lines of therapy including at least one prior platinum-based chemotherapy:
- Patients with recurrent endometrial cancer that has failed at least one line of platinum-based chemotherapy;
- Patients with newly diagnosed advanced (metastatic and/or unresectable) disease has persist lesion after frontline treatment with surgery and platinum-based chemotherapy ± radiotherapy;
- Patients with newly diagnosed advanced disease that is not amenable to curative treatment with surgery and/or radiation therapy cannot tolerate chemotherapy;
- Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
- Histologically proven diagnosis of endometrial cancer.
Show all 21Show fewer
- Tumors must demonstrate MMRd and MLH1 methylation.
- ° Endometrial tumor MMR and MLH1 methylation status: All participants must be screened using Immunohistochemistry (IHC) for MMR proteins MLH1, MSH2, MSH6, and PMS2. MLH1 gene promoter methylation is performed in tumors exhibiting MLH1 and/or PMS2 IHC loss. MLH1 methylation status is determined by the bisulfite mediated detection of methylated cytosines, as described by Benhamida (Benhamida JK, et al. Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform. J Mol Diagn. 2020 Mar;22:368-375. doi: 10.1016/j.jmoldx.2019.11.005).
- All patients must have measurable disease by RECIST 1.1.
- ECOG performance status 0-2.
- Life expectancy ≥ 12 weeks.
- Patients must have adequate organ function:
- Absolute neutrophil count (ANC) ≥ 1.5×10^9/L;
- Platelet count ≥ 70 × 10^9/L;
- Hemoglobin ≥ 80 g/L;
- Total bilirubin ≤ 1.5 x 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);
- Creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula);
- Baseline albumin ≥ 25 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)
- Signed and dated informed consent.
Who cannot join
- Histologically confirmed diagnosis of sarcoma components including malignant mixed mullerian tumors.
- Patients who have had prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
- History of severe hypersensitivity reaction (≥Grade 3) to any monoclonal antibody.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Uncontrolled hypertension (blood pressure >140/90 mmHg) after adequate treatment.
- Central nervous system diseases, including uncontrollable epilepsy and central nervous system metastases.
Show all 23Show fewer
- Radiographically confirmed major blood vessel invasion/infiltration.
- Prior chemotherapy, targeted small molecule therapy, bevacizumab, or radiation therapy within 4 weeks of study Day 1 or not recovered from adverse events caused by previously administered treatment.
- Prior hormonal therapy for the treatment of endometrial carcinoma within 1 weeks of study Day 1.
- Known history of Human Immunodeficiency Virus (HIV).
- Known active tuberculosis (TB, Bacillus tuberculosis).
- Known active Hepatitis B or C.
- known active ulcer, or active colitis.
- Received live vaccine within 30 days of planned start of study treatment.
- Patients who have gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of anlotinib.
- Patients who have severe gastrointestinal or non-gastrointestinal fistula (≥Grade 3).
- Patients who have an allogenic tissue/solid organ transplant.
- Patients who have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- ⁕⁕⁕Note:
- Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted;
- Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents are permitted;
- A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted;
- Is pregnant or breastfeeding.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Camrelizumab Plus Anlotinib in Patients With Recurrent Sporadic Mismatch Repair Deficient Endometrial Cancer (CAN-RESPOND): a Single-arm, Multicentre, Phase 2 Study
Patients with advanced mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) endometrial cancer (EC) are currently treated as one entity, and immune checkpoint inhibitor (ICI) monotherapy is the treatment of choice. However, different molecular mechanisms drive the development of dMMR/MSI-H tumors, including germline mutations in canonical MMR genes (Lynch syndrome), somatically acquired MMR gene mutations (Lynch-like), and homozygous methylation of the MLH1 gene promoter (sporadic). There is increasing evidence that patients with sporadic MMRd EC have a worse response to ICI monotherapy than those with Lynch/Lynch-like tumors. Antiangiogenic therapy can relieve immunosuppression through blood vessel normalization and the oxygen metabolism pathway, thereby having a synergistic effect with ICIs. Anlotinib is an oral anti-angiogenic tyrosine kinase inhibitor (TKI). Camrelizumab is a fully humanized, high-affinity monoclonal antibody against PD-1. The purpose of this trial is to assess the efficacy and safety and tolerability of anlotinib plus camrelizumab in recurrent EC patients with sporadic MMRd tumors.
- Conditions
- Endometrial Cancer
- Being tested
- Anlotinib + Camrelizumab
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib + CamrelizumabDrug
Anlotinib PO plus Camrelizumab IV
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib + Camrelizumab | Experimental | Anlotinib 12 mg QD p.o for 2 weeks and then stop for 1 week plus Camrelizumab 200 mg (fixed dose) IV every 3 weeks (+/- 3 days) until progression or adverse effects prohibit therapy Receives: Drug: Anlotinib + Camrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.
Measured: 24 months
Secondary outcomes (5)
Frequency and severity of adverse events (AEs)
Number of participants with AEs occurring up to 28 days after the last administration are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
Measured: 24 months
Progression-free Survival (PFS)
The duration from date of enrollment to the disease progression, death, or the date of last contact, whichever occurs first.
Measured: 24 months
Overall Survival (OS)
The duration from date of enrollment to time of death or the date of last contact, , whichever occurs first.
Measured: 24 months
Disease Control Rate (DCR)
The percentage of participants in the analysis population who have a CR, PR or SD as assessed by RECIST 1.1.
Measured: 24 months
Duration of Response (DOR)
the time from first documented CR or PR until disease progression or death due to any cause, whichever occurs first.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start1 Nov 2022 (estimated)
- Primary completion30 Nov 2025 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yan-fang Ye, PhD, Study director, Clinical Research Design Division, Sun Yat-sen Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05550558
- Sponsor's protocol ID
- 2021-KY-111
- Acronym
- CAN-RESPOND
- Status last verified
- Apr 2022
- First submitted
- 20 Sep 2022
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The protocol and statistical analysis plan will be made available on Clinicaltrials.gov.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Camrelizumab Plus Anlotinib in Patients With Recurrent Sporadic Mismatch Repair Deficient Endometrial Cancer (CAN-RESPOND): a Single-arm, Multicentre, Phase 2 Study
- ClinicalTrials.gov ID
- NCT05550558
- Acronym / sponsor ID
- CAN-RESPOND / 2021-KY-111
- Conditions
- Endometrial Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Nov 2022 (estimated)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 22 Sep 2022 (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.
Patients with advanced mismatch repair-deficient (MMRd) or microsatellite instability-high (MSI-H) endometrial cancer (EC) are currently treated as one entity, and immune checkpoint inhibitor (ICI) monotherapy is the treatment of choice. However, different molecular mechanisms drive the development of dMMR/MSI-H tumors, including germline mutations in canonical MMR genes (Lynch syndrome), somatically acquired MMR gene mutations (Lynch-like), and homozygous methylation of the MLH1 gene promoter (sporadic). There is increasing evidence that patients with sporadic MMRd EC have a worse response to ICI monotherapy than those with Lynch/Lynch-like tumors. Antiangiogenic therapy can relieve immunosuppression through blood vessel normalization and the oxygen metabolism pathway, thereby having a synergistic effect with ICIs. Anlotinib is an oral anti-angiogenic tyrosine kinase inhibitor (TKI). Camrelizumab is a fully humanized, high-affinity monoclonal antibody against PD-1. The purpose of this trial is to assess the efficacy and safety and tolerability of anlotinib plus camrelizumab in recurrent EC patients with sporadic MMRd tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib + Camrelizumab | Experimental | Drug: Anlotinib + CamrelizumabAnlotinib 12 mg QD p.o for 2 weeks and then stop for 1 week plus Camrelizumab 200 mg (fixed dose) IV every 3 weeks (+/- 3 days) until progression or adverse effects prohibit therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients must receive have completed at least 1 but no more than 3 prior lines of therapy including at least one prior platinum-based chemotherapy:
- Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
- Histologically proven diagnosis of endometrial cancer.
- Tumors must demonstrate MMRd and MLH1 methylation.
- ° Endometrial tumor MMR and MLH1 methylation status: All participants must be screened using Immunohistochemistry (IHC) for MMR proteins MLH1, MSH2, MSH6, and PMS2. MLH1 gene promoter methylation is performed in tumors exhibiting MLH1 and/or PMS2 IHC loss. MLH1 methylation status is determined by the bisulfite mediated detection of methylated cytosines, as described by Benhamida (Benhamida JK, et al. Reliable Clinical MLH1 Promoter Hypermethylation Assessment Using a High-Throughput Genome-Wide Methylation Array Platform. J Mol Diagn. 2020 Mar;22:368-375. doi: 10.1016/j.jmoldx.2019.11.005).
Key exclusion criteria (23 listed)
- Histologically confirmed diagnosis of sarcoma components including malignant mixed mullerian tumors.
- Patients who have had prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
- History of severe hypersensitivity reaction (≥Grade 3) to any monoclonal antibody.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Uncontrolled hypertension (blood pressure >140/90 mmHg) after adequate 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 |
|---|---|---|
| Anlotinib + CamrelizumabAnlotinib PO plus Camrelizumab IV | Drug | Anlotinib + Camrelizumab |
Primary outcome
Objective response rate (ORR)
Time frame: 24 months
ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria.
5 secondary outcomes
Frequency and severity of adverse events (AEs)
Time frame: 24 months
Progression-free Survival (PFS)
Time frame: 24 months
Overall Survival (OS)
Time frame: 24 months
Disease Control Rate (DCR)
Time frame: 24 months
Duration of Response (DOR)
Time frame: 24 months
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 28 Sep 2022.
- Individual participant dataSharing planned: Yes. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov.
Related trials for Endometrial Cancer
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Active, not recruitingPhase 3
Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line
Endometrial Cancer
RecruitingPhase 3
Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer
Advanced Endometrial Carcinoma, Recurrent Endometrial Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 3
Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Stage I Endometrial Cancer
Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
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.
Yan-fang Ye, PhD study director
Clinical Research Design Division, Sun Yat-sen Memorial Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anlotinib + Camrelizumab in people with Endometrial Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.
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 21 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: opening soon, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
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 Jing Li, MD (008602034071260, lijing228@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 24 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 28 Sep 2022.