Perioperative Toripalimab and Endostatin for Stage II Melanoma: A Phase II Trial

NCT06965231 | Recruiting Phase 2 DMC

• 1 other identifier: IRB2501312-12
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase II clinical trial to evaluate the efficacy and safety of perioperative toripalimab (anti-PD-1) combined with recombinant human endostatin (Endostar) as postoperative adjuvant therapy in patients with clinical stage II cutaneous or acral malignant melanoma. The study aims to answer:

1. 1.Does this combination improve the 2-year recurrence-free survival (2y-RFS) compared to historical data?
2. 2.Is the treatment safe and tolerable for patients?
3. 3.Receive 2 cycles of toripalimab before surgery (neoadjuvant therapy).
4. 4.Undergo surgical removal of the tumor.
5. 5.Post surgery, receive toripalimab every 2 weeks + Endostar (72-hour continuous infusion every 4 weeks) for up to 6 cycles (Endostar) or 11 cycles (toripalimab).
6. 6.Be monitored for tumor recurrence, side effects, and survival for up to 2 years after treatment.

Conditions

Melanoma of Skin; Acral Melanoma; Stage II Melanoma

Keywords

Melanoma of skin; Acral melanoma; Stage II melanoma; Toripalimab; Recombinant human endostatin (Endostar); Perioperative immunotherapy; PD-1 inhibitor; Anti-angiogenic therapy; Phase II study

Outcome Measures

Primary Outcomes (1)

• 2-year recurrence-free survival rate (2-year RFS rate)

  From enrollment to the end of the 2nd year of follow-up

Secondary Outcomes (4)

• 1-year distant metastasis-free survival rate (1-year DMFS rate)

  From enrollment to the end of the 1st year

• Overall survival (OS)

  Through study completion, an average of 3 years

• 1-year recurrence-free survival rate (1-year RFS rate)

  From enrollment to the end of the 1st year

• 2-year distant metastasis-free survival rate (2-year DMFS rate)

  From enrollment to the end of the 2nd year

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Participants will: 1. Receive 2 cycles of toripalimab before surgery (neoadjuvant therapy). 2. Undergo surgical removal of the tumor. 3. Post surgery, receive toripalimab every 2 weeks + Endostar (72-hour continuous infusion every 4 weeks) for up to 6 cycles (Endostar) or 11 cycles (toripalimab). 4. Be monitored for tumor recurrence, side effects, and survival for up to 2 years after treatment.

Drug: Toripalimab combined with Endostar

Interventions

Toripalimab combined with Endostar DRUG

1. Neoadjuvant Phase: 2 doses of toripalimab (240 mg IV, Q2W) before surgery. 2. Surgery: Tumor resection within 2 weeks after the last neoadjuvant dose. 3. Adjuvant Phase: 1) Toripalimab: 240 mg IV every 2 weeks (up to 11 cycles); 2) Endostar: 210 mg (72-hour continuous IV infusion) every 4 weeks (up to 6 cycles).

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, regardless of gender;
• ECOG performance status: 0-1;
• Patients with histologically or cytologically confirmed cutaneous or acral malignant melanoma, excluding mucosal and uveal melanoma;
• Patients with BRAF, CKIT, and NRAS gene test results;
• Treatment-naïve patients who have not received prior anti-tumor therapy;
• Clinical stage II (AJCC 8th edition, 2017);
• Laboratory tests must meet the following criteria:
• Hematology: Hemoglobin (Hb) ≥90 g/L (no transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×10\^9/L; platelet count (PLT) ≥100×10\^9/L;
• Biochemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN; serum creatinine (Cr) ≤1.5×ULN, and creatinine clearance \>50 μmol/L;
• Coagulation: Activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤1.5×ULN;
• Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%;
• Female patients must agree to use contraception (e.g., intrauterine device \[IUD\], oral contraceptives, or condoms) during the study and for 6 months after study completion. A negative serum or urine pregnancy test within 7 days before enrollment is required, and patients must be non-lactating. Male patients must agree to use contraception during the study and for 6 months after study completion;
• Patients must voluntarily participate in the study, sign the informed consent form, and demonstrate good compliance.

You may not qualify if:

• History of allergic reactions to biological products;
• Patients with prior or concurrent malignancies within 5 years (except cured basal cell carcinoma of skin or carcinoma in situ of cervix);
• Any active autoimmune disease or history of autoimmune disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; asthma requiring bronchodilators for medical intervention). Exceptions include: vitiligo, psoriasis, alopecia not requiring systemic therapy, well-controlled type I diabetes, or hypothyroidism with normal thyroid function on replacement therapy;
• Requirement for immunosuppressive therapy using systemic or absorbable topical corticosteroids (equivalent to prednisone \>10mg/day) within 2 weeks prior to first dose;
• Any history or evidence of bleeding diathesis regardless of severity; grade ≥3 bleeding events per CTCAE v5.0 within 4 weeks prior to first dose; or presence of unhealed wounds, fractures, active gastrointestinal ulcers, ulcerative colitis, tumors with active bleeding, or other conditions deemed by investigators to potentially cause gastrointestinal hemorrhage or perforation;
• Patients with severe and/or uncontrolled comorbidities including:
• Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥90 mmHg);
• Unstable angina, myocardial infarction, ≥grade 2 congestive heart failure, or arrhythmias requiring treatment (including QTc ≥480ms) within 6 months prior to first dose;
• Active or uncontrolled severe infections (≥grade 2 per CTCAE);
• Clinically significant liver disease including viral hepatitis (active HBV infection with HBV DNA \>1×10³ copies/mL or \>500 IU/mL; HCV infection with HCV RNA \>1×10³ copies/mL or \>100 IU/mL), decompensated liver disease, or chronic hepatitis requiring antiviral therapy;
• HIV-positive status;
• Poorly controlled diabetes (fasting glucose ≥grade 2 per CTCAE);
• Urinalysis showing proteinuria ≥++ with 24-hour urinary protein \>1.0 g;
• Administration of live vaccines within 4 weeks prior to treatment or anticipated need during study;
• Other conditions deemed by investigators to potentially lead to premature study termination, including: severe comorbidities (including psychiatric disorders) requiring concomitant therapy, significant laboratory abnormalities, or social/family factors that may compromise patient safety or data/sample collection.

Sponsors & Collaborators

• Fudan University: lead
• Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai 411 hospital: collaborator

Study Sites (4)

Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Cancer center, Shanghai 411 hospital, China RongTong Medical Healthcare Group Co.Ltd./411 Hospital, Shanghai University

Shanghai, Shanghai Municipality, 200081, China

RECRUITING

Department of Surgical Oncology, Fudan University Shanghai Cancer Center Minhang Branch Hospital

Shanghai, Shanghai Municipality, 200240, China

RECRUITING

Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200336, China

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

endostar protein

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Chunmeng Wang, Dr.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunmeng Wang, Dr.

CONTACT

+86 13671976170; cmwang1975@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: Director, Head of Musculoskeletal Oncology, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: April 18, 2025
• First Posted: May 11, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: May 11, 2025

Record last verified: 2025-05

Locations

CN (4)