TIP (Paclitaxel + Ifosfamide + Cisplatin) Combined With Nimotuzumab & Triprilimab as Neoadjuvant Treatment in Locally Advanced Penile Cancer

A Single Center and Single Arm Study of TIP (Paclitaxel + Ifosfamide + Cisplatin) Combined With Nimotuzumab & Triprilimab as Neoadjuvant Treatment in Locally Advanced Penile Cancer

Primary Objective:To evaluate the efficacy and safety of TIP (paclitaxel + ifosfamide + cisplatin) combined with nimotuzumab & triprilimab as neoadjuvant treatment in locally advanced penile cancer.

Study Overview

• Status: Completed
• Conditions: Penile Cancer
• Intervention / Treatment: Drug: Albumin-Bound Paclitaxel; Drug: Ifosfamide; Drug: Cisplatin; Drug: Nimotuzumab; Drug: Triprilimab

Detailed Description

Penile cancer is a rare malignant tumor, which often occurs in the inner plate of prepuce and glans. Squamous cell carcinoma is the most common pathological type. Lymph node metastasis is a crucial factor that leads to poor prognosis of penile cancer. The 5-year OS of penile cancer patients without lymph node metastasis is 90%. Still, it goes down sharply in patients with inguinal lymph node metastasis and pelvic lymph node metastasis, which is 50% and 0%, respectively.

Using neoadjuvant chemotherapy to treat patients with locally advanced penile cancer (T4, any N stage, or any T stage, N3) may improve their prognosis. TIP (Paclitaxel + Ifosfamide + Cisplatin) regimen is the first line neoadjuvant treatment recommended by NCCN guidelines. Epidermal growth factor receptor (EGFR) plays a vital role in the development of penile cancer. It's also an important therapeutic target for penile cancer. PD-1 is an immune checkpoint molecule on the surface of T cells. In recent years, immune-checkpoint inhibitors targeting PD-1 have shown good efficacy in a variety of tumors. Some phase II / III clinical trials have shown that PD-1 inhibitors can improve the prognosis of patients with lung squamous cell carcinoma, head and neck squamous cell carcinoma and cervical cancer. Previous studies have found that PD-L1 is highly expressed in 40% - 60% of penile cancer, suggesting that penile cancer patients may benefit from immunotherapy.

The management of penile cancer with lymph node metastasis is difficult, especially for N2-3 stage. This phase II study aim to explore an effective combination therapy for locally advanced penile cancer. 29 patients need to be enrolled.TIP & nimotuzumab & triprilimab will be administered per 21-day until surgery, evidence of disease progression or onset of unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Squamous cell carcinoma confirmed by histology or cytology;
2. Clinical Stage is Locally advanced penile cancer (T4, any N stage; or any T stage, N3);
3. No prior chemotherapy for newly diagnosed or relapsed patients;
4. There is at least one measurable lesion according to the solid tumor efficacy evaluation standard RECIST1.1;
5. the Eastern Cooperative Oncology Group (ECOG) scored 0-2;
6. Blood marrow function: Hemoglobin(Hb) >/= 80g/L; White blood cell count >/= 3.0x10^9/L; Neutrophil count >/= 1.5x10^9/L; Platelet count >/= 100x10^9/L;
7. Liver function: AST, ALT, ALP </= 2.5 ULN; Total bilirubin </= 1.5 ULN;
8. Estimated survival >/= 12 months;
9. No prior serious disease history of systemic organ;
10. The participant unterstand this study procedure and sign the informed consent.

Exclusion Criteria:

1. Peripheral neuropathy degree >/=2 (affecting patient's function);
2. Previously received any other experimental drug treatment within 4 weeks before enrollment;
3. Patients with other cancer at present, or have other malignent tumor history within past 5 years. Except for: (1) Cured skin non-malignant melanoma; (2) Curable tumor, including low-risk prostate cancer (T1a, Gleason score<6, PSA<0.5ng/ml), superficial bladder cancer and so on; (3) Other solid tumors have received radical treatment, and no recurrence or metastasis has been found at least 5 years;
4. Other serious or poorly controlled concomitant diseases, including but not limited to: (1) Severe or acute attack disease history of cardiovascular, liver, respiratory, kidney, blood ,endocrine or neuropsychiatric system within 6 months; (2) Active infection history and needed antibiotic treatment within 2 weeks before enrollment; (3) Congestive heart failure (grade III-IV); (4) Unstable angina pectoris or myocardial infarction history within 6 months.

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: Neoadjuvant Therapy; TIP (Paclitaxel + Ifosfamide + Cisplatin) & Nimotuzumab & Triprilimab	Drug: Albumin-Bound Paclitaxel; 260 mg/m² IV over 30 minutes on Day 1; Drug: Ifosfamide; 1200 mg/m² IV over 2 hours on Days 1-3; Drug: Cisplatin; 25 mg/m² IV over 2 hours on Days 1-3; Drug: Nimotuzumab; 400 mg IV on Day 1; Drug: Triprilimab; 240 mg IV on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathologically Complete Response	Histopathologic assessment for patients undergoing surgical resection followed by 4 cycles of neoadjuvant treatment. Pathologically complete response is defined as the absence of noninvasive tumor residuals in inguinal lymph node and pelvic lymph node after neoadjuvant chemotherapy as assessed by American Joint Committee on Cancer (AJCC) staging version 8.0.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	6 weeks
Progression Free Survival (PFS)	Progression free survival is defined as the time from the randomization to tumor progression or death due to any cause.	2 months
Overall Survival (OS)	Overall survival is defined as the time from randomization to death due to any cause.	6 months
Adverse events	Number of participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.	2-months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): May 6, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Penile Diseases; Penile Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Cisplatin; Ifosfamide; Albumin-Bound Paclitaxel; Nimotuzumab
• Other Study ID Numbers: B2020-103-01

Drug and device information, study documents

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