Camrelizumab Combined With Chemotherapy and Apatinib for Extrapulmonary Neuroendocrine Carcinomas

NCT05142865 | Unknown Phase 2

• 1 other identifier: MA-NEC-Ⅱ-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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）

Conditions

Advanced or Metastatic EP-NEC

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (5)

• Overall survival (OS)

  3 years

• Progression-Free Survival (PFS)

  3 years

• Duration of Response (DOR)

  3 years

• Disease Control Rate (DCR)

  2 years

• Adverse event (AE)

  2 years

Study Arms (1)

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 .

Drug: Camrelizumab; Drug: Etoposide; Drug: Carboplatin; Drug: Cisplatin; Drug: Apatinib

Interventions

Camrelizumab DRUG

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.

Also known as: SHR-1210

Camrelizumab+ Chemotherapy+Apatinib

Etoposide DRUG

100mg/m2 IV continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6)

Camrelizumab+ Chemotherapy+Apatinib

Carboplatin DRUG

AUC 5 mg/mL/min IV on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6)

Camrelizumab+ Chemotherapy+Apatinib

Cisplatin DRUG

25mg/m2，continuously on Day 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6)

Camrelizumab+ Chemotherapy+Apatinib

Apatinib DRUG

250 mg given orally, once daily in 21-day cycle

Camrelizumab+ Chemotherapy+Apatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.
• 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;

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Huazhong University of Science and Technology: lead

Study Sites (1)

Tongji Hospital，Tongji Medical College Affiliated，Huazhong University of Science ＆ Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Interventions

camrelizumab; Etoposide; Carboplatin; Cisplatin; apatinib

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Hong Qiu, MD

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

• Yuhong Dai, MD

  Tongji Hospital

  STUDY DIRECTOR

Central Study Contacts

Hong Qiu, MD

CONTACT

13986296106; qiuhong@hust.edu.cn

Yuhong Dai, MD

CONTACT

13476229575; eier_dai@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 3, 2021
• Study Start: January 14, 2022
• Primary Completion: January 14, 2024
• Study Completion: December 31, 2024
• Last Updated: December 3, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)