Neuroendocrine Carcinoma of the BladderPhase 2/3NCT03992911
Safety and Efficacy of FOLFSIM Plus Toripalimab in the Treatment of Advanced or Metastatic Neuroendocrine Carcinoma
A Phase 2/3 study testing Simmtecan, 5-FU and l-LV, Toripalimab and Etoposide, Cisplatin in people with Neuroendocrine Carcinoma of the Bladder, run by Peking University at 1 site in China.
Trial summary
This study is designed as Phase II/III. Phase II is aimed to evaluate safety and efficacy of Simmtecan and the 5-FU/LV regimen (FOLFSIM regimen) plus Toripalimab. Phase III is aimed to verify inferiority of the overall survival of FOLFSIM regimen plus Toripalimab in comparison with EP/EC in advanced or metastatic… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuroendocrine Carcinoma of the Bladder
- What is being tested?
- Simmtecan, 5-FU and l-LV, Toripalimab and Etoposide, Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 1 siteChina
- Study dates
- 19 Jun 2019to 20 Jun 2023
- Phase
- Phase 2/3
- 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
- Signed informed-consent form.
- Male and Female aged between 18-75 years.
- Histologically confirmed locally advanced or metastatic nonfunctional poorly-differentiated G3 neuroendocrine carcinoma(NEC), including small cell NEC, large cell NEC and MANEC.
- Unresectable, including local advanced, recurrent or metastatic disease:
- Patients who had progressed after first-line platinum-based regimen or intolerance for treatment, or unwilling to receive current standard chemotherapy (only for phase II); Patients who has received no systemic chemotherapy, or relapsed at least 6 months since completion of adjuvant chemotherapy or radiotherapy.
- At least 1 measurable lesion according to RECIST criteria;
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- Providing with tumor specimen (for testing the expression of PD L1 and the infiltrating lymphocytes);
- Eastern Cooperative Oncology Group (ECOG) 0-1;
- Adequate liver, kidney and bone marrow function; Screening laboratory values must meet the following criteria: hemoglobin ≥ 10.0 g/dL; neutrophils ≥ 1500 cells/ μL; platelets ≥ 100 x 10^3/ μL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1.5 x ULN, creatinine clearance >60ml/min (CockcroftGault equation), INR≤1.5, APTT≤1.5 x ULN;
Who cannot join
- Histologically confirmed well differentiated G3 neuroendocrine tumor;
- Evidence with active CNS disease or epilepsy;
- Metastasis over 5 lesions;
- Prior treatment with CPT-11 or antiPD1/PDL1/CTLA-4 antibody for neoadjuvant or adjuvant therapy;
- Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix;
- Predicted survival <3 months;
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- Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II NYHA, heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm);
- Any uncontrollable active infection, within past 1 week
- Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
- History with tuberculosis;
- The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and other tolerable events determined by investigator;
- Hypersensitivity to Simmtecan or recombinant humanized antiPD1 monoclonal Ab or its components;
- Prior antitumor therapy (including chemotherapy, target therapy, corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
- Patients who received a potent inhibitor or inducer of CYP3A4 within 1 week prior to the first dose;
- Prior radical radiothearpy within past 4 weeks;
- Prior major surgery within past 4 weeks (diagnostic surgery excluded);
- Prior live vaccine therapy within past 4 weeks;
- Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (>500IU/ml);
- Pregnant or nursing;
- Males or female of childbearing potential refuse to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
- Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Shen Lin, Professor, 010-88196561, Linshenpku@163.com
Shen Lin, professor
About this study
Official title: Phase II/III Trial of Simmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab Versus EP/EC in Advanced or Metastatic Neuroendocrine Carcinoma
This study is designed as Phase II/III. Phase II is aimed to evaluate safety and efficacy of Simmtecan and the 5-FU/LV regimen (FOLFSIM regimen) plus Toripalimab. Phase III is aimed to verify inferiority of the overall survival of FOLFSIM regimen plus Toripalimab in comparison with EP/EC in advanced or metastatic neuroendocrine cancer.
Read the detailed description
This is a Phase II/III, randomized, two-part, multi-center study, in which subjects with advanced or metastatic neuroendocrine carcinoma will be enrolled.
This study will be conducted in two parts:
Part 1, the Phase II study was to: (i) evaluate the safety and tolerability of the FOLFSIM regimen plus Toripalimab; and (ii) identify the recommended dose; (iii) assess the antitumor activity; (iv) the pharmacokinetic (PK) parameters of the drugs in the regimen.
Part 2, the Phase III study was to verify inferiority of FOLFSIM regimen plus Toripalimab compared with the current standard chemotherapy (EP/EC regimen) in the first-line treatment of advanced or metastatic neuroendocrine carcinoma.
- Conditions
- Neuroendocrine Carcinoma of the Bladder
- Being tested
- Simmtecan, 5-FU and l-LV, Toripalimab, Etoposide, Cisplatin, Etoposide, Carboplatin
- Keywords
- Neuroendocrine Carcinoma, Simmtecan, Toripalimab
- Medical subject headings
- Carcinoma, Neuroendocrine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simmtecan, 5-FU and l-LVDrug
Also called FOLFSIM regimen
Simmtecan was administered intravenously at 80 mg per square meter on day1 with LV 400 mg per square meter administered as a 2-hour infusion, and 5-FU 2400 mg per square meter as a 46-hour infusion on day1 every 2 weeks in one course.
ToripalimabDrug
Also called JS001
Toripalimab was administered intravenously at 240 mg on day 1 every 2 weeks in one course.
Etoposide, CisplatinDrug
Also called EP regimen
Etoposide was administered intravenously at 100 mg per square meter on day 1,2,3 with Cisplatin at 80 mg per square meter on day 1 every 3 weeks in one course.
Etoposide, CarboplatinDrug
Also called EC regimen
Etoposide was administered intravenously at 100 mg per square meter on day 1,2,3 and Carboplatin with AUC 5mg/mL/min on day 1 every 3 weeks in one course.
| Study group | Role | What they receive |
|---|---|---|
| FOLFSIM Plus Teripalimab | Experimental | Simmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab Receives: Drug: Simmtecan, 5-FU and l-LV; Drug: Toripalimab |
| EP/EC | Active comparator | Etoposide plus Cisplatin or Carboplatin Receives: Drug: Etoposide, Cisplatin; Drug: Etoposide, Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measure of time from study treatment to patient's death or lost to follow-up.
Measured: 2 years
Secondary outcomes (5)
Progression-free survival
Measure of time from study treatment to disease progression or death.
Measured: 2 years
Objective response rate
Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)
Measured: 2 years
Disease control rate
The sum of rates of partial response, complete response and steady disease based on Response Evaluation Criteria In Solid Tumors (RECIST).
Measured: 2 years
Duration of response
Duration of Response by RECIST
Measured: 2 years
The incidence of treatment related emergent adverse events（Safety and Tolerance)
Adverse reactions evaluation is based on the CTCAE
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 posted20 Jun 2019
- Study start19 Jun 2019
- Primary completion20 Jun 2022 (estimated)
- Study completion20 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine Carcinoma of the BladderStudies of the same condition, open and under way.
- More trials run by Peking 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 336 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shen Lin, Peking University
- Investigators
- Lin Shen, Principal investigator, Peking University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03992911
- Sponsor's protocol ID
- LP-201
- Status last verified
- Jun 2019
- First submitted
- 19 Jun 2019
- Last updated
- 20 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Trial of Simmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab Versus EP/EC in Advanced or Metastatic Neuroendocrine Carcinoma
- ClinicalTrials.gov ID
- NCT03992911
- Acronym / sponsor ID
- LP-201
- Conditions
- Neuroendocrine Carcinoma of the Bladder
- Keywords
- Neuroendocrine Carcinoma, Simmtecan, Toripalimab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 336 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Study start
- 19 Jun 2019 (actual)
- Primary completion
- 20 Jun 2022 (estimated)
- Study completion
- 20 Jun 2023 (estimated)
- First posted
- 20 Jun 2019 (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 study is designed as Phase II/III. Phase II is aimed to evaluate safety and efficacy of Simmtecan and the 5-FU/LV regimen (FOLFSIM regimen) plus Toripalimab. Phase III is aimed to verify inferiority of the overall survival of FOLFSIM regimen plus Toripalimab in comparison with EP/EC in advanced or metastatic neuroendocrine cancer.
Detailed description
This is a Phase II/III, randomized, two-part, multi-center study, in which subjects with advanced or metastatic neuroendocrine carcinoma will be enrolled.
This study will be conducted in two parts:
Part 1, the Phase II study was to: (i) evaluate the safety and tolerability of the FOLFSIM regimen plus Toripalimab; and (ii) identify the recommended dose; (iii) assess the antitumor activity; (iv) the pharmacokinetic (PK) parameters of the drugs in the regimen.
Part 2, the Phase III study was to verify inferiority of FOLFSIM regimen plus Toripalimab compared with the current standard chemotherapy (EP/EC regimen) in the first-line treatment of advanced or metastatic neuroendocrine carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFSIM Plus Teripalimab | Experimental | Drug: Simmtecan, 5-FU and l-LV, Drug: ToripalimabSimmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab |
| EP/EC | Active comparator | Drug: Etoposide, Cisplatin, Drug: Etoposide, CarboplatinEtoposide plus Cisplatin or Carboplatin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed informed-consent form.
- Male and Female aged between 18-75 years.
- Histologically confirmed locally advanced or metastatic nonfunctional poorly-differentiated G3 neuroendocrine carcinoma(NEC), including small cell NEC, large cell NEC and MANEC.
- Unresectable, including local advanced, recurrent or metastatic disease:
- Patients who had progressed after first-line platinum-based regimen or intolerance for treatment, or unwilling to receive current standard chemotherapy (only for phase II); Patients who has received no systemic chemotherapy, or relapsed at least 6 months since completion of adjuvant chemotherapy or radiotherapy.
Key exclusion criteria (21 listed)
- Histologically confirmed well differentiated G3 neuroendocrine tumor;
- Evidence with active CNS disease or epilepsy;
- Metastasis over 5 lesions;
- Prior treatment with CPT-11 or antiPD1/PDL1/CTLA-4 antibody for neoadjuvant or adjuvant therapy;
- Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix;
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 |
|---|---|---|
| Simmtecan, 5-FU and l-LVAlso: FOLFSIM regimenSimmtecan was administered intravenously at 80 mg per square meter on day1 with LV 400 mg per square meter administered as a 2-hour infusion, and 5-FU 2400 mg per square meter as a 46-hour infusion on day1 every 2 weeks in one course. | Drug | FOLFSIM Plus Teripalimab |
| ToripalimabAlso: JS001Toripalimab was administered intravenously at 240 mg on day 1 every 2 weeks in one course. | Drug | FOLFSIM Plus Teripalimab |
| Etoposide, CisplatinAlso: EP regimenEtoposide was administered intravenously at 100 mg per square meter on day 1,2,3 with Cisplatin at 80 mg per square meter on day 1 every 3 weeks in one course. | Drug | EP/EC |
| Etoposide, CarboplatinAlso: EC regimenEtoposide was administered intravenously at 100 mg per square meter on day 1,2,3 and Carboplatin with AUC 5mg/mL/min on day 1 every 3 weeks in one course. | Drug | EP/EC |
Primary outcome
Overall survival
Time frame: 2 years
Measure of time from study treatment to patient's death or lost to follow-up.
5 secondary outcomes
Progression-free survival
Time frame: 2 years
Objective response rate
Time frame: 2 years
Disease control rate
Time frame: 2 years
Duration of response
Time frame: 2 years
The incidence of treatment related emergent adverse events（Safety and Tolerance)
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 20 Jun 2019.
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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.
Lin Shen principal investigator
Peking University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Simmtecan, 5-FU and l-LV, Toripalimab and Etoposide, Cisplatin in people with Neuroendocrine Carcinoma of the Bladder, run by Peking 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 9 inclusion and 21 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 20 Jun 2019. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Lin Shen (86-10-88196561, linshenpku@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (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 20 Jun 2019.