Nab-PCE vs PC for MM After Failure of Anti-PD-1

Nab-paclitaxel Plus Carboplatin Combined Endostatin Versus Solvent-based Paclitaxel Plus Carboplatin in the Treatment of Advanced Melanoma After the Failure of PD-1 Treatment #A Randomized Controlled, Open, Multicenter Trial

This is a randomized controlled clinical trial of nab-paclitaxel + carboplatin

• Endostatin for advanced melanoma after failure of PD-1 therapy. The aim was to evaluate the efficacy and safety of nab-paclitaxel+carboplatin
• endostatin versus combination of paclitaxel and carboplatin in patients with advanced melanoma after failure of PD-1 therapy.

Study Overview

• Status: Unknown
• Conditions: Advanced Melanoma
• Intervention / Treatment: Drug: Chemotherapeutic Combinations; Drug: chemotherapy

Detailed Description

The enrollment time is expected to be 1.5 year and the observation time is 2 years. The regimen were performed on a 28-day/21-day cycle respectively. Subjects who met the entry criteria were treated in a 2:1 group according to a randomized list: the treatment group was treated with nab-paclitaxel + carboplatin + endostatin regimen, and the control group was treated with paclitaxel + carboplatin. In this trial, the efficacy is evaluated every 8 weeks until disease progression or unacceptable toxicity,or until the investigator deemed that the patient's condition was unacceptable for further treatment. The follow-up period was 24 months after the end of treatment (follow-up patient survival information and new anti-tumor treatment). The planning enrolled sample size for nab-paclitaxel + carboplatin + endostatin group and paclitaxel-carboplatin group were 90 patients and 45 patients, respectively.

• Study Type: Interventional
• Enrollment (Anticipated): 145
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lili Mao, Dr.; Phone Number: 861013261859885; Email: yunzhongmanbu7848@163.com
• Study Contact Backup: Name: Lu Si, Dr.; Phone Number: 861088196956

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lili Mao, Dr; Phone Number: 861013261859885; Email: yunzhongmanbu7848@163.com
      • Contact: Lu Si; Phone Number: 861088196956

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years old, ≤ 70 years old, male or female;
2. Histological or pathological diagnosis of advanced melanoma, and progressed after anti-PD-1 treatment (disease progression or unacceptable toxicity);
3. The patient has at least one (RECIST 1.1 standard) measurable lesion, which needs to be detected by spiral CT or MRI, and the tumor lesion has at least one single diameter ≥ 1 cm;
4. ECOG PS is 0 or 1 (see Annex 1 for standards);
5. The estimated survival period is ≥12 weeks;
6. no chemotherapy contraindications, including normal peripheral blood, liver and kidney function and electrocardiogram are basically normal; Peripheral blood: neutrophils ≥1.5×109/L, platelets≥90×109/ L, hemoglobin≥90 g/L; Renal function: normal serum creatinine; For patients with non-metastatic liver function impairment: alanine, aspartate aminotransferase ≤ 2.5 ULN, For patients with metastatic liver dysfunction: alanine, aspartate aminotransferase ≤ 5 ULN;
7. Patients who have undergone topical treatment for asymptomatic brain metastases can be enrolled and have a clinical stable status of at least 4 weeks.
8. Patients voluntarily participate in and sign an informed consent form.
9. contraindications for the use of no carboplatin, paclitaxel, entropic and albumin paclitaxel

Exclusion Criteria:

1. Known HIV, hepatitis B/C virus positive status or history of active tuberculosis (testing prior to randomisation is not required)
2. Received any investigational drug within 28 days or 5 half-lives of the planned first dose of this study treatment.
3. Active infection requiring systemic therapy.
4. A known history of another malignancy or concurrent malignancy unless the patient is disease-free for a minimum of 1 year, is completely treated and is at low-risk of recurrence.
5. Patients with a history or evidence of cardiovascular risk,
6. History or evidence of interstitial lung disease or active non-infectious pneumonitis.
7. Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.
8. Pregnant or breastfeeding females, or expecting to conceive or father children within the projected period of study treatment (52 weeks followed by 4 months following end of study treatment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nab-paclitaxel + endostatin+ carboplatin; nab-paclitaxel + endostatin+ carboplatin nab-paclitaxel 260mg/m2, d1 +Carboplatin AUC=5, d1 +endostatin 15mg, d1-14 q28d	Drug: Chemotherapeutic Combinations; nab-paclitaxel 260mg/m2 d1+Carboplatin AUC=5 d1+ endostatin 15mg d1-14，q28d
Active Comparator: paclitaxel+carboplatin; paclitaxel+carboplatin paclitaxel 175 mg/m2, d1+ Carboplatin AUC=5, d1 q21d	Drug: chemotherapy; paclitaxel 175 mg/m2 d1+Carboplatin AUC=5 d1, q21d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	The time from treatment to tumor progression or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	response evaluation disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria. response (PR), refers to the number of cases with complete and partial response after treatment as a percentage of the total number of evaluable cases	At the end of Cycle 2 (each cycle is 28 days)
Disease Control Rate (DCR)	The disease control rate was the proportion of patients with complete remission, partial remission and stability (SD) in all patients.	At the end of Cycle 2 (each cycle is 28 days)
overall survival (OS)	OS was defined as the time from the date of the first administration of trial regimen to the date of death from any cause (event) or last follow-up (censored data).	3 years
Adverse events (AE)	Adverse events (AE) were monitored on an ongoing basis and classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. Patients were assessed for toxicities before each administration, and toxicity was graded accordingly	3 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Jun Guo, Dr., Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2019
• Primary Completion (Anticipated): September 30, 2021
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: carboplatin; melanoma; nab-paclitaxel; endostatin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2019NPCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available.
• IPD Sharing Time Frame: Data will be available within 6 months of study completion.
• IPD Sharing Access Criteria: data access requests will be reviewed by an external Independent Review Panel.Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No