Neoadjuvant Toripalimab in Combination With Carboplatin and Nab-paclitaxel in Untreated Salivary Gland Malignant Neoplasms

NCT04825938 | Not Yet Recruiting Phase 2

• 1 other identifier: 003
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This proposed study will evaluate the efficacy and safety of preoperative administration Toripalimab combined with nab-paclitaxel and carboplatin in salivary gland malignant neoplasms who are about to undergo surgery.Monoclonal antibodies, such as Toripalimab , may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.This trial will be helpful for comprehensive exploratory characterization of tumor immune microenvironment and circulating immune cells in these patients.

Conditions

Salivary Gland Malignant Neoplasms; Salivary Gland Tumors

Outcome Measures

Primary Outcomes (2)

• Adverse events graded by CTCAE v5.0

  Percentage of adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).

  90 days after the first dose of study treatment

• Percentage of participants demonstrating pathological response

  Pathologic response in the primary tumor was assessed using a quantitative grading scheme: pathologic tumor response \[nonviable tumor\] PTR0 = no or \<10% PTR1 = ≥10% PTR2 = ≥50%

  At time of surgery

Secondary Outcomes (5)

• Disease-free survival （DFS）

  2 years

• Overall survival（OS）

  5 years

• Radiographic Response

  5 weeks

• Pathologic Response

  6 weeks

• Rate of surgery delay

  8 weeks after the patient receives their last dose

Study Arms (1)

Toripalimab + Carboplatin + Nab-paclitaxel

EXPERIMENTAL

* Toripalimab (IV), dose= 240mg , day=1 , cycle length: 21 days. * Carboplatin (IV), dose=300mg/m2, day= 1, cycle length: 21 days. * Nab-paclitaxel (IV), dose=260mg/m2, day= 1, cycle length: 21 days.

Drug: Toripalimab , Carboplatin, Nab-paclitaxel

Interventions

Toripalimab , Carboplatin, Nab-paclitaxel DRUG

Patients receive toripalimab IV on day 1, paclitaxel IV on day 1 and carboplatin IV on day 1 . Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Toripalimab + Carboplatin + Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of salivary gland cancers which is planned for treatment with curative intent including surgical resection: mucoepidermoid carcinoma, adenocarcinoma, adenoidcystic carcinoma, acinic cell carcinoma, or other histology .
• Greater than or equal to 18 and less than 80 years of age at time of study entry.
• ECOG performance status of 0 or 1.
• Measurable disease as per RECIST 1.1.
• Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines.
• Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
• Adequate hepatic and renal function as demonstrated by
• Serum creatinine \< 1.5 X ULN or CrCl \> 40mL/min (if using the Cockcroft-Gault formula below):
• Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL)）
• Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL))x 0.85
• AST/ALT ≤ 3 x ULN
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Adequate bone marrow function as demonstrated by:
• Absolute Neutrophil Count \>1,500/µL
• Platelets \> 100 X 103/µL

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had another known invasive malignancy within the previous 5 years and/or has had surgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5 years for a known malignancy prior to study day 0.
• If subject received major surgery for any other reason, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -5. Inhaled or topical steroids, and adrenal replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids.
• Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger .
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to the treatment or other agents used in the study.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
• Has known active Hepatitis B or C.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Interventions

toripalimab; Carboplatin; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Central Study Contacts

Song Fan, Doctor degrees

CONTACT

13570536658; fansong2@mail.sysu.edu.cn

Tingting Cai, Bachelor's Degrees

CONTACT

17520060409; caitt23@mail2.sysu.edu.cn

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: Associate Professor

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 1, 2021
• Study Start: April 30, 2021
• Primary Completion: June 1, 2022
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

CN (1)