Advanced or Metastatic EP-NECPhase 2NCT05142865
Camrelizumab Combined With Chemotherapy and Apatinib for Extrapulmonary Neuroendocrine Carcinomas
A Phase 2 study testing Camrelizumab, Etoposide and Carboplatin in people with Advanced or Metastatic EP-NEC, run by Huazhong University of Science and Technology at 1 site in China.
Trial summary
This is an open-label，single-arm, phase II exploratory study that evaluates the efficacy and safety of Camrelizumab combined with Chemotherapy （carboplatin or cisplatin + etoposide）and Apatinib as First Line treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC） Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced or Metastatic EP-NEC
- What is being tested?
- Camrelizumab, Etoposide and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 14 Jan 2022to 31 Dec 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible patients for this study must meet all of the following criteria:
- Pathologically or cytologically diagnosed as locally advanced or metastases extrapulmonary neuroendocrine carcinoma that cannot be surgically removed.
- Aged 18-75，male and female
- Patients who have not received systemic treatment for advanced or metastatic EP-NEC . Subjects who have previously received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy or radiochemotherapy) for EP-NEC must have completed the last dose at least 6 months before enrollment . Palliative radiotherapy is permitted, but it must be completed at least 2 weeks prior to the study treatment. The lesions in the irradiation field cannot be used as target lesions for efficacy evaluation, and radiotherapy-related adverse reactions must be restored to at least Grade 0-1.
- ECOG PS 0-1.
- At least 1 measurable lesion according to RECIST criteria.
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- Adequate organ and bone marrow function, defined as follows:
- White blood cell count (WBC) ≥ 3,000/mm3 (3.0 × 109/L);
- Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 109/L);
- Platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L);
- Hemoglobin (Hb) ≥ 9 g/dL (90 g/L);
- Serum albumin ≥ 3.0 g/dL (30 g/L);
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min;
- Total bilirubin (BIL) ≤ 1.5 x ULN;
- AST or ALT ≤ 2.5 x ULN, patients with liver metastases should ≤ 5×ULN; international normalized ratio (INR) ≤ 1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
- Urine protein<2+; if the urine protein is ≥2+, the 24-hour urine protein must be ≤1g.
- Subjects must agree and have signed the informed consent form, be willing and able to follow the scheduled visits, study treatment, laboratory tests, and other study procedures.
- Life expectancy > 12 weeks.
- Female subjects of childbearing age are not pregnant or breastfeeding and are strictly contraceptive.
Who cannot join
- Presence of known uncontrolled or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. For CNS metastases that have been adequately treated, and neurological symptoms can return to baseline levels at least 2 weeks before enrollment (except for residual signs or symptoms related to CNS treatment), they can be included . In addition, subjects must stop corticosteroids or receive a stable dose of ≤ 10 mg/d or a gradually decreasing dose of prednisone (or an equivalent dose of other corticosteroids) at least 2 weeks before enrollment.
- Have received the following treatments or drugs before enrollment:
- ① A major operation was performed within 28 days before enrollment (tissue biopsy and peripheral venipuncture for central venous catheterization [PICC]/infusion port implantation are allowed).
- ② Using immunosuppressive drugs within 7 days before enrollment, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/d prednisone or other corticosteroids with equivalent physiological doses)
- ③ within 28 days before enrollment or planned to receive live attenuated vaccine during the study period and 60 days after the end of study drug treatment.
- ④ Receive chemotherapy within 28 days before enrollment;
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- Prior malignancy within 3 years, except adequately treated basal cell carcinoma or squamous cell skin cancer ,superficial bladder cancer, cervical carcinoma in situ, breast ductal carcinoma in situ and papillary thyroid cancer.
- Prescence of any active, known or suspected autoimmune diseases. Subjects who are in a stable state and do not require systemic immunosuppressive therapy are allowed, such as type I diabetes, hypothyroidism that only requires hormone replacement therapy, and skin diseases that do not require systemic therapy (eg, vitiligo, psoriasis disease and hair loss).
- Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies that act on T cell costimulation or checkpoint pathways.
- Prescence of clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment; gastrointestinal perforation and/or gastrointestinal fistula occurred within 6 months before enrollment; 6 before enrollment Arterial/venous thrombosis events that occurred within a month, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
- Have major vascular disease (for example, an aortic aneurysm that requires surgical repair or recent peripheral arterial thrombosis) occurred within 6 months before the start of study treatment.
- Severe, unhealed or dehisced wounds and active ulcers or untreated fractures.
- Have intestinal obstruction and/or have clinical signs or symptoms of gastrointestinal obstruction within 6 months before the start of the study treatment.
- Prescence of interstitial lung disease, non-infectious pneumonia or uncontrollable systemic disease.
- Known to be allergic to the study drug or any of its excipients; or have a severe allergic reaction to other monoclonal antibodies.
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; hepatitis C,defined as HCV-RNA higher than the detection limit of the analytical method) or combined hepatitis B and C co-infection.
- Any of the following conditions observed within 6 months prior to the enrollment: myocardial infarction, severe/unstable angina, NYHA grade 2 or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure exhaustion.
- Hypertension, which cannot be well controlled by antihypertensive drugs (systolic blood pressure> 140 mmHg or diastolic blood pressure> 90 mmHg).
- Systemic use of antibiotics for ≥ 7 days within 4 weeks before enrollment, or unexplained fever > 38.5 ° C during screening / before the first administration (according to the judgment of the investigator, fever caused by tumor can be enrolled) .
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Participated in any other drug clinical research within 4 weeks before enrollment, or no more than 5 half-lives from the last drug use in the study. Known history of psychotropic drug abuse or drug abuse.
- Subjects with other severe physical or psychiatric disorders or laboratory abnormalities, which may increase the risk of participating in this study or interfere with the study results, as well as those deemed unsuitable by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site
Tongji Hospital，Tongji Medical College Affiliated，Huazhong University of Science ＆ Technology
Wuhan, Hubei, 430030
About this study
Official title: A Phase II Clinical Study Evaluating the Safety and Efficacy of Camrelizumab Combined With Chemotherapy and Apatinib as First Line Treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
This is an open-label，single-arm, phase II exploratory study that evaluates the efficacy and safety of Camrelizumab combined with Chemotherapy （carboplatin or cisplatin + etoposide）and Apatinib as First Line treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
- Conditions
- Advanced or Metastatic EP-NEC
- Being tested
- Camrelizumab, Etoposide, Carboplatin, Cisplatin, Apatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CamrelizumabDrug
Also called SHR-1210
Camrelizumab intravenous infusion was administered at a dose of 200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6) and maintenance phase ,until PD.
EtoposideDrug
100mg/m2 IV continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6)
CarboplatinDrug
AUC 5 mg/mL/min IV on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6)
CisplatinDrug
25mg/m2，continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6)
ApatinibDrug
250 mg given orally, once daily in 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Camrelizumab+ Chemotherapy+Apatinib | Experimental | Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle . Receives: Drug: Camrelizumab; Drug: Etoposide; Drug: Carboplatin; Drug: Cisplatin; Drug: Apatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate （ORR）
Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the investigator according to the RECIST 1.1
Measured: 2 years
Secondary outcomes (5)
Overall survival (OS)
OS is defined as the time from registration to death due to any cause.
Measured: 3 years
Progression-Free Survival (PFS)
PFS is defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.
Measured: 3 years
Duration of Response (DOR)
For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by the investigator or death due to any cause, whichever occurs first.
Measured: 3 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease per RECIST 1.1
Measured: 2 years
Adverse event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2021
- Study start14 Jan 2022 (estimated)
- Primary completion14 Jan 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic EP-NECStudies of the same condition, open and under way.
- More trials run by Huazhong University of Science and TechnologyThe 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huazhong University of Science and Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xianglin Yuan, Huazhong University of Science and Technology
- Investigators
- Hong Qiu, MD, Principal investigator, Tongji HospitalYuhong Dai, MD, Study director, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05142865
- Sponsor's protocol ID
- MA-NEC-Ⅱ-001
- Status last verified
- Nov 2021
- First submitted
- 22 Nov 2021
- Last updated
- 3 Dec 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 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Study Evaluating the Safety and Efficacy of Camrelizumab Combined With Chemotherapy and Apatinib as First Line Treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
- ClinicalTrials.gov ID
- NCT05142865
- Acronym / sponsor ID
- MA-NEC-Ⅱ-001
- Conditions
- Advanced or Metastatic EP-NEC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 14 Jan 2022 (estimated)
- Primary completion
- 14 Jan 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 3 Dec 2021 (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.
This is an open-label，single-arm, phase II exploratory study that evaluates the efficacy and safety of Camrelizumab combined with Chemotherapy （carboplatin or cisplatin + etoposide）and Apatinib as First Line treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Camrelizumab+ Chemotherapy+Apatinib | Experimental | Drug: Camrelizumab, Drug: Etoposide, Drug: Carboplatin, Drug: Cisplatin, Drug: ApatinibInduction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle . |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Eligible patients for this study must meet all of the following criteria:
- Pathologically or cytologically diagnosed as locally advanced or metastases extrapulmonary neuroendocrine carcinoma that cannot be surgically removed.
- Aged 18-75，male and female
- Patients who have not received systemic treatment for advanced or metastatic EP-NEC . Subjects who have previously received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy or radiochemotherapy) for EP-NEC must have completed the last dose at least 6 months before enrollment . Palliative radiotherapy is permitted, but it must be completed at least 2 weeks prior to the study treatment. The lesions in the irradiation field cannot be used as target lesions for efficacy evaluation, and radiotherapy-related adverse reactions must be restored to at least Grade 0-1.
- ECOG PS 0-1.
Key exclusion criteria (22 listed)
- Presence of known uncontrolled or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. For CNS metastases that have been adequately treated, and neurological symptoms can return to baseline levels at least 2 weeks before enrollment (except for residual signs or symptoms related to CNS treatment), they can be included . In addition, subjects must stop corticosteroids or receive a stable dose of ≤ 10 mg/d or a gradually decreasing dose of prednisone (or an equivalent dose of other corticosteroids) at least 2 weeks before enrollment.
- Have received the following treatments or drugs before enrollment:
- ① A major operation was performed within 28 days before enrollment (tissue biopsy and peripheral venipuncture for central venous catheterization [PICC]/infusion port implantation are allowed).
- ② Using immunosuppressive drugs within 7 days before enrollment, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/d prednisone or other corticosteroids with equivalent physiological doses)
- ③ within 28 days before enrollment or planned to receive live attenuated vaccine during the study period and 60 days after the end of study drug 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 |
|---|---|---|
| CamrelizumabAlso: SHR-1210Camrelizumab intravenous infusion was administered at a dose of 200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6) and maintenance phase ,until PD. | Drug | Camrelizumab+ Chemotherapy+Apatinib |
| Etoposide100mg/m2 IV continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6) | Drug | Camrelizumab+ Chemotherapy+Apatinib |
| CarboplatinAUC 5 mg/mL/min IV on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6) | Drug | Camrelizumab+ Chemotherapy+Apatinib |
| Cisplatin25mg/m2，continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6) | Drug | Camrelizumab+ Chemotherapy+Apatinib |
| Apatinib250 mg given orally, once daily in 21-day cycle | Drug | Camrelizumab+ Chemotherapy+Apatinib |
Primary outcome
Overall response rate （ORR）
Time frame: 2 years
Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the investigator according to the RECIST 1.1
5 secondary outcomes
Overall survival (OS)
Time frame: 3 years
Progression-Free Survival (PFS)
Time frame: 3 years
Duration of Response (DOR)
Time frame: 3 years
Disease Control Rate (DCR)
Time frame: 2 years
Adverse event (AE)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 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.
Hong Qiu, MD principal investigator
Tongji Hospital
Yuhong Dai, MD study director
Tongji Hospital
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 Camrelizumab, Etoposide and Carboplatin in people with Advanced or Metastatic EP-NEC, run by Huazhong University of Science and Technology 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 19 inclusion and 22 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 3 Dec 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 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 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 Hong Qiu, MD (13986296106, qiuhong@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate （ORR） (time frame: 2 years). 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 Dec 2021.