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Neoadjuvant Anti-PD-1 and TP Versus TPF on Pathological Response in OSCC

Primary Purpose

Oral Squamous Cell Carcinoma, Neoadjvant Therapy, Anti-PD-1

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Toripalimab (anti-programmed death-1 inhibitor)

Albumin paclitaxel

Cisplatin

Docetaxel

5-Fluorouracil

About this trial

This is an interventional treatment trial for Oral Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: 18-75 years old
Gender: male and female
Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-2
Histopathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheek, floor of mouth, hard palate, and posterior molar region)
Primary tumor with a clinical stage of III/IVA (T1-2/N1-2/M0 or T3-4a/cN0-2/M0, AJCC2018)
Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Blood routine: white blood cells (WBCs) >3,000/mm3, hemoglobin >8 g/L, platelets >80,000/mm3
Liver function: alanine amino transferase/aspartate amino transferase (ALAT/ASAT) <2.5 times the upper limit of normal and bilirubin <1.5 times the upper limit of normal
Renal function: Serum creatinine <1.5 times the upper limit of normal
Coagulation function: INR, PT, APTT<1.5 times the upper limit of normal
Signed the informed consent form

Exclusion Criteria:

Unresolved grade 2 [(Common Terminology Criteria for Adverse Events (CTCAE 5.0)] or higher toxic reactions caused by previous anticancer treatments
Known allergic reaction to any ingredients or excipients of the therapy
Known history of malignancy, unless been cured and no recurrence for 5 years
Known history of radiation to head and neck
Active severe clinical infection (> National Cancer Institute (NCI)-CTCAE version 5.0 grade 2 infection)
Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, grade 2 or higher heart disease diagnosed according to the New York Heart Association (NYHA) classification 3 months before enrollment]
Patients receiving immunology-based treatment for any reason
Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy
Pregnant or lactating women
Uncontrollable hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >90 mmHg) or cardiovascular diseases with clinical significance (such as activity), such as cerebrovascular accidents (≤ 6 months before screening), myocardial infarction (≤6 months before screening), unstable angina pectoris, NYHA grade II or above congestive heart failure, or severe arrhythmia that cannot be controlled by drugs or has a potential impact on trial treatment
Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation
Participation in other clinical trials within 30 days before enrollment
Other situations that the investigator considers unsuitable with respect to participating in the trial

Sites / Locations

Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Neoadjuvant TTP

Neoadjuvant TPF

Arm Description

The participants will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD-1 inhibitor, 240 mg) on d1 and d22.

The participants will receive two cycles of intravenous Docetaxel (75 mg/m^2) on d1 and d22, Cisplatin (75 mg/m^2) on d1 and d22, and 5-Fluorouracil (750 mg/m^2/day) for 5 days (d1-5 and d22-26), the interval is 16±1 days.

Outcomes

Primary Outcome Measures

Major pathologic response

The major pathologic response (MPR): the percentage of tumor cells before and after treatment was compared according to biopsy specimens before neoadjuvant therapy and pathological specimens after surgery; the percentage of residual viable tumor (RVT) cells was evaluated on resected tumor slides. MPR was defined as ≤ 10% RVT%.

Secondary Outcome Measures

2-year disease-free survival rate

Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.

2-year overall survival rate

Overall survival was calculated from the date of randomization to death from any cause.

Full Information

NCT ID

NCT05125055

First Posted

November 17, 2021

Last Updated

October 8, 2022

Sponsor

Shanghai Jiao Tong University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT05125055

Brief Title

Neoadjuvant Anti-PD-1 and TP Versus TPF on Pathological Response in OSCC

Official Title

Neoadjuvant Toripalimab and Albumin Paclitaxel /Cisplatin Versus Docetaxel/ Cisplatin/ 5-fluorouracil (TPF) on Pathological Response in Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 1, 2021 (Actual)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai Jiao Tong University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

To compare the pathological efficacy of neoadjuvant Toripalimab and Albumin paclitaxel /Cisplatin (TTP) with Docetaxel/ Cisplatin/ 5-flurouracil (TPF) for patients with locally advanced resectable oral squamous cell carcinoma (OSCC), and to determine the safety of neoadjuvant TTP. In order to explore a better protocol of neoadjuvant therapy to improve the efficacy in patients with locally advanced OSCC.

Detailed Description

In the previous "Illuminate" trial, neoadjuvant anti-programmed death-1 (PD-1) of Toripalimab and Albumin paclitaxel /Cisplatin (TTP) therapy was used in 20 patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), and the neoadjuvant therapy was well-tolerated. The major pathologic response (MPR) rate was 60% (12/20), including 30% (6/20) pathological complete response (pCR). Furthermore, the MPR might transfer to survival benefit in the patients received neoadjuvant therapy. Therefore, in this randomized trial, we aimed to compare the pathological response of neoadjuvant TTP therapy versus TPF chemotherapy in the patients with locally advanced OSCC (Illuminate-2 trial). A total of 80 patients will be enrolled in this trial, and the primary endpoint is MPR rate. The neoadjuvant TTP arm will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD1 inhibitor, 240 mg) on d1 and d22, followed by the standard treatment of surgery and postoperative adjuvant therapy. The neoadjuvant TPF arm will received two cycles of intravenous Docetaxel (75mg/m^2), Cisplatin (75mg/m^2) on d1 (d22), and 5-Fu(750mg/m^2/day) for 5 days (d1-5 and d22-26), followed by the standard treatment of surgery and postoperative adjuvant therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Oral Squamous Cell Carcinoma, Neoadjvant Therapy, Anti-PD-1, Chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant TTP

Arm Type

Experimental

Arm Description

The participants will receive two cycles of intravenous Albumin paclitaxel (260mg/ m^2), Cisplatin (75mg/ m^2) and Toripalimab (anti-PD-1 inhibitor, 240 mg) on d1 and d22.

Arm Title

Neoadjuvant TPF

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Toripalimab (anti-programmed death-1 inhibitor)

Intervention Description

The participants will receive two cycles of Toripalimab, with 21 days each. 240mg of Toripalimab will be used intravenously on the first day of each cycle.

Intervention Type

Drug

Intervention Name(s)

Albumin paclitaxel

Intervention Description

The participants will receive two cycles of Albumin paclitaxel, with 21 days each. 260mg/m^2 of Albumin paclitaxel will be used intravenously on the first day of each cycle.

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

The participants will receive two cycles of Cisplatin, with 21 days each. 75mg/m^2 of Cisplatin will be used intravenously on the first day of each cycle.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

The participants will receive two cycles of Docetaxel, with 21 days each. 75mg/m^2 of Docetaxel will be used intravenously on the first day of each cycle.

Intervention Type

Drug

Intervention Name(s)

5-Fluorouracil

Intervention Description

The participants will receive two cycles of 5-Fluorouracil, with 21 days each. 750mg/m^2/d of 5-Fluorouracil will be used as a 120-hour continuous intravenous infusion on days 1 through 5.

Primary Outcome Measure Information:

Title

Major pathologic response

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

2-year disease-free survival rate

Description

Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.

Time Frame

24 months

Title

2-year overall survival rate

Description

Overall survival was calculated from the date of randomization to death from any cause.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: 18-75 years old Gender: male and female Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-2 Histopathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheek, floor of mouth, hard palate, and posterior molar region) Primary tumor with a clinical stage of III/IVA (T1-2/N1-2/M0 or T3-4a/cN0-2/M0, AJCC2018) Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Blood routine: white blood cells (WBCs) >3,000/mm3, hemoglobin >8 g/L, platelets >80,000/mm3 Liver function: alanine amino transferase/aspartate amino transferase (ALAT/ASAT) <2.5 times the upper limit of normal and bilirubin <1.5 times the upper limit of normal Renal function: Serum creatinine <1.5 times the upper limit of normal Coagulation function: INR, PT, APTT<1.5 times the upper limit of normal Signed the informed consent form Exclusion Criteria: Unresolved grade 2 [(Common Terminology Criteria for Adverse Events (CTCAE 5.0)] or higher toxic reactions caused by previous anticancer treatments Known allergic reaction to any ingredients or excipients of the therapy Known history of malignancy, unless been cured and no recurrence for 5 years Known history of radiation to head and neck Active severe clinical infection (> National Cancer Institute (NCI)-CTCAE version 5.0 grade 2 infection) Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, grade 2 or higher heart disease diagnosed according to the New York Heart Association (NYHA) classification 3 months before enrollment] Patients receiving immunology-based treatment for any reason Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy Pregnant or lactating women Uncontrollable hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >90 mmHg) or cardiovascular diseases with clinical significance (such as activity), such as cerebrovascular accidents (≤ 6 months before screening), myocardial infarction (≤6 months before screening), unstable angina pectoris, NYHA grade II or above congestive heart failure, or severe arrhythmia that cannot be controlled by drugs or has a potential impact on trial treatment Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation Participation in other clinical trials within 30 days before enrollment Other situations that the investigator considers unsuitable with respect to participating in the trial

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lai-ping Zhong, MD, PhD

Phone

+862123271699

Ext

5160

zhonglp@hotmail.com

Facility Information:

Facility Name

Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

20011

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lai-ping Zhong, MD, PhD

Phone

+86-21-23271699

Ext

5160

zhonglaiping@163.com

First Name & Middle Initial & Last Name & Degree

Lai-ping Zhong, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The study protocol and the primary study report might be shared depending on the condition of trial completion.

Learn more about this trial

Neoadjuvant Anti-PD-1 and TP Versus TPF on Pathological Response in OSCC

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