Nab-paclitaxel Combined With Bevacizumab in the Treatment of Metastatic Neuroendocrine Carcinoma

• ClinicalTrials.gov Identifier: NCT04705519
• Recruitment Status: Recruiting
• First Posted: January 12, 2021
• Last Update Posted: January 12, 2021
• Sponsor: Peking University
• Collaborator: Qilu Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Shen Lin, Peking University

Study Description

Brief Summary:

This is an open-label, phase II study evaluating efficacy and safety of Nab-paclitaxel Combined With Bevacizumab for unresectable Recurrent or metastatic neuroendocrine carcinoma.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Carcinoma	Drug: Nab-paclitaxel Combined With Bevacizumab	Phase 2

Detailed Description:

Nab-paclitaxel Combined With Bevacizumab will be evaluated in participants who have had ≥ 1 line of previous treatment. The primary endpoint is the Overall Survival (OS).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Non-randomized, Multicenter, Phase II Study of Nab-paclitaxel Combined With Bevacizumab for Unresectable Recurrent or Metastatic Neuroendocrine Carcinoma
• Actual Study Start Date: January 5, 2021
• Estimated Primary Completion Date: January 5, 2022
• Estimated Study Completion Date: January 5, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nab-paclitaxel Combined With Bevacizumab; Nab-paclitaxel, Bevacizumab	Drug: Nab-paclitaxel Combined With Bevacizumab; Nab-paclitaxel 150mg/m2 ，iv drip, d1, Bevacizumab 5mg/kg, iv drip, d1, q2w.

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: an expected average of 24 months ]
   Duration from the date of initial treatment to the date of death due to any cause

Secondary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
   Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
2. Duration of Response (DoR) [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
   The percentage of patients who achieve complete remission(CR) or partial remission (PR) or stable disease(SD) determined by the RECIST v1.1 criteria.
3. Progression Free Survival (PFS) [ Time Frame: an expected average of 24 months ]
   A duration from the date of initial treatment to radiographic disease progression or death of any cause
4. Disease Control Rate (DCR) [ Time Frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
   Proportion of objective complete response, partial response and stable patients
5. Adverse events [ Time Frame: an expected average of 24 months ]
   Including other occasional or rare AEs

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients who provided written informed consent to be subjects in this trial
2. Aged ≥18 years
3. Has histologically-confirmed diagnosis of locally advanced unresectable or metastatic neuroendocrine carcinoma
4. Has received and progressed on ≥1 prior systemic therapy for their advanced disease.
5. Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
6. Have measurable disease as defined by RECIST 1.1 as determined by investigator assessment
7. Agree to provide tumor tissue sample deemed adequate for histopathology confirmation

8. Adequate Organ Function Laboratory Values:

   Hemoglobin ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelets ≥80×109/L; AST and ALT ≤ 1.5 ULN or ≤ 3 ULN for subjects with liver metastases; Total bilirubin ≤1.5 ULN; Serum creatinine ≤1.5 ULN or measured or calculated creatinine clearance > 50ml/min; Albumin ≥ 30g/L;

9. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication and must be willing to use an adequate method of contraception for the course of the study through 90 days after the last dose of study medication. Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy

Exclusion Criteria:

1. Patients have recovered adverse events associated with pretreatment to Grade 1 or lower with CTCAE v5.0 excluding alopecia
2. Patients have an active malignancy (except for definitively treated basal cell carcinoma of the skin, or carcinoma-in-situ of the cervix) within the past 5 years
3. Patients with uncontrolled central nervous system metastasis
4. Received anti-tumor therapy within 4 weeks, including: chemotherapy (the washout period of oral fluorouracil drugs is 2 weeks), targeted therapy (the washout period of small molecule targeted drugs is 2 weeks or 5 half-lives, whichever is shorter), immunotherapy, etc.;
5. Received radical radiotherapy (including >25% bone marrow radiotherapy) and brain radiotherapy within 4 weeks; brachytherapy (such as implantation of radioactive particles) within 60 days; received palliative radiotherapy for bone metastases within 1 week;
6. Patients with a history of prior treatment with docetaxel, paclitaxel, nab-paclitaxel or bevacizumab
7. Received surgery within 4 weeks or unhealed wounds, Ulcers, fractures;
8. Uncontrollable malignant pleural effusion, ascites, or pericardial effusion (defined as the investigator's judgment cannot be effectively controlled by diuretics or puncture);
9. Patients have gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or other conditions judged that may cause gastrointestinal bleeding or perforation;
10. Patients with evidence or medical history of thrombosis or obvious bleeding tendency within 2 months (bleeding> 30 mL within 2 months, hematemesis, melena, blood in the stool), hemoptysis (> 5 mL of fresh blood within 4 weeks);
11. Patients have arterial thrombosis or deep vein thrombosis occurred within 6 months; or stroke and/or transient ischemic attack occurred within 12 months;
12. Active heart disease that is not well controlled, e.g. symptomatic coronary heart disease, New York Heart Association (NYHA) congestive heart failure of grade II or above, severe arrhythmias requiring drug intervention, myocardial infarction within the past 6 months, LVEF<50%
13. Patients judged with clinically significant electrolyte abnormalities
14. Patients have an active infection or an unexplained fever (temperature> 38.5℃) during the screening period or before the first administration
15. Patients with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year
16. Is pregnant or breastfeeding
17. Patients were judged unsuitable as subjects of this trial by investigators.

Contacts and Locations

Contacts

Contact: Lin Shen, Professor; 86-10-88196561; linshenpku@163.com

Locations

China, Beijing

Beijing Cancer Hospital; Recruiting

Beijing, Beijing, China, 100142

Contact: Lin Shen 86-10-88196561 linshenpku@163.com

Sponsors and Collaborators

Peking University

Qilu Pharmaceutical Co., Ltd.

More Information

• Responsible Party: Shen Lin, Professor, Peking University
• ClinicalTrials.gov Identifier: NCT04705519
• Other Study ID Numbers: CGOG3006/NEC-BEVAX
• First Posted: January 12, 2021
• Last Update Posted: January 12, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Neuroendocrine; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Paclitaxel; Bevacizumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors