The Efficacy and Safety of Neoadjuvant Toripalimab Combined With Temozolomide in Resectable Stage III Melanoma

The Efficacy and Safety of Neoadjuvant Toripalimab Combined With Temozolomide in Resectable Stage III Melanoma: A Prospective, Single-center, Phase 2 Clinical Trial

This study is being conducted to explore the efficacy and safety of neoadjuvant toripalimab combined with temozolomide in resectable stage III melanoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma Stage III
• Intervention / Treatment: Drug: Toripalimab combined with Temozolomide

Detailed Description

This trial is a prospective, single-center, single-arm clinical research. Unlike seen in Caucasians, checkpoint inhibitors have not obtained satisfactory results in Chinese patients. Exploring the curative effects of combination therapies in melanoma and their potential synergetic mechanism will improve the prognosis of patients. Recent retrospective data in our center showed that the objective response rate (ORR) of immunotherapy plus chemotherapy in advanced melanoma reached 40%, which was higher than immunotherapy (12.5%) and chemotherapy (4%) alone as front-line therapies. This study is aiming to evaluate the efficacy and safety of toripalimab combined with temozolomide in patients with resectable stage III melanoma. The safety and efficacy of this study will be assessed through ORR, DCR, PFS, OS, and adverse effects as graded by CTCAE 5.0.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yong Chen, MD; Phone Number: 18017317571; Email: chenyong@fudan.edu.cn

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Yong Chen, MD; Phone Number: 18017317571; Email: chenyong@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has resectable stage IIIB-IIID melanoma of acral and cutaneous type, according to American Joint Committee on Cancer (AJCC) staging system version 8. At least one measurable lesion conforming to RECIST 1.1 criteria.
• No previously received systematic therapy of anti-PD-1 plus temozolomide. For patients with relapsed melanoma, previous therapy of anti-PD-1 plus temozolomide has been stopped for more than 6 months is acceptable.

For patients with disease progressed after receiving immune checkpoint inhibitors only, time from the last treating day is ≥ 4 weeks.

• The toxicity of prior treatment has recovered to ≤1 grade according to CTCAE 5.0.
• ECOG score 0-1.
• The expected survival time is ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Female subjects of childbearing age must undergo a serum pregnancy test within 7 days before the commencement of the study and the results are negative, and are willing to use a medically approved high potency contraceptive method during the study period and within 3 months after the last administration of the study drug; For male subjects whose partner is a female of childbearing age, they should be surgically sterilized or agree to use an effective method of contraception during the study period and for 3 months after administration of the last study.
• Willing to consent and signed the informed consent, and able comply with the planned visit, research treatment, laboratory examination and other test procedures.

Exclusion Criteria:

• Has mucosal melanoma or choroidal melanoma.
• The first study drug treatment was less than 4 weeks from the last systematic antitumor therapy or 5 half-lives from the last targeted therapy; less than 4 weeks from major surgery; less than7 days from immunosuppressive drug; less than 3 weeks from immunomodulatory; less than 4 weeks from live attenuated vaccine.
• Systemic antibiotic use for 7 days within 4 weeks prior to initial administration, or unexplained fever during screening/prior to initial administration.
• With active autoimmune disease or a history of autoimmune disease.
• With history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• With immunodeficiency, eg HIV, HBV, HCV.
• Have a clear history of serious and uncontrolled other disease or mental disorders.
• Has a bleeding tendency or abnormal clotting function.
• Known to be allergic to the active ingredients or excipients in this study.
• Other situations that the researcher considers inappropriate to participate in the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toripalimab Combined With Temozolomide	Drug: Toripalimab combined with Temozolomide; Toripalimab combined with Temozolomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic response rate (pRR)	After 2 cycles of neoadjuvant toripalimab combined with temozolomide, patients receive radical surgery.	Within one week after operation

Collaborators and Investigators

• Sponsor: Yong Chen
• Investigators: Principal Investigator: yong chen, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: April 9, 2023
• First Submitted That Met QC Criteria: April 23, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: FU-Name-T004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No