Pembrolizumab Plus Chemo in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma (Eastern Cooperative Thoracic Oncology Projects 2004, ECTOP-2004)

NCT ID: NCT05281003

Last Updated: 2023-07-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-20

Study Completion Date

2026-09-01

Brief Summary

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The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and paclitaxel as neoadjuvant treatment in participants with locally advanced esophageal squamous cell carcinoma (ESCC), and to explore treatment resistance mechanisms.

Detailed Description

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The overall primary efficacy hypotheses are as follows:

In all eligible participants with locally advanced ESCC, pathologic complete response (pCR) rate is non-inferior with pembrolizumab plus SOC chemotherapy compared with historical benchmark.

The overall primary translational hypotheses are as follows:

Major hypoxia signals are significantly higher in baseline or post-treatment tumor samples from non-responders to pembrolizumab plus SOC chemotherapy, as compared to those samples from responders.

Conditions

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Esophageal Squamous Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Pembrolizumab in combination with chemotherapy (Paclitaxel plus Cisplatin, TP regimen)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pembrolizumab + Chemo

Neoadjuvant setting (Pembrolizumab in combination with chemotherapy): Up to 4 cycles concurrent administrations of (1) Paclitaxel, which are administrated intravenously at 150 mg/m\^2 dosage on Day 1 of each 3-week cycle; (2) Cisplatin, which are administrated intravenously at 80 mg/m\^2 dosage on Day 1 of each 3-week cycle; (3) Pembrolizumab, which are administrated intravenously at 200 mg dosage on Day 1 of each 3-week cycle.

Adjuvant setting (Pembrolizumab in combination with chemotherapy): All participants who are assessed as ineligible or unnecessary for surgery after neoadjuvant treatment may be eligible for up to an additional 17 cycles (approximately 1 year) of Pembrolizumab treatment in combination with chemotherapy.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Biological: Pembrolizumab 200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Paclitaxel

Intervention Type DRUG

Drug: Paclitaxel 150 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Cisplatin

Intervention Type DRUG

Drug: Cisplatin 80 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Interventions

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Pembrolizumab

Biological: Pembrolizumab 200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Intervention Type DRUG

Paclitaxel

Drug: Paclitaxel 150 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Intervention Type DRUG

Cisplatin

Drug: Cisplatin 80 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Intervention Type DRUG

Other Intervention Names

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Keytruda MK-3475

Eligibility Criteria

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Inclusion Criteria

\[Participants are eligible to be included in the study only if all of the following criteria apply\]

1. Male/female participants who are at least 18 years of age on the day of providing documented informed consent with histologically or cytologically confirmed diagnosis of locally advanced and surgically resectable cT2-T4a NX M0 esophageal squamous cell carcinoma (ESCC) (per AJCC 8th edition) and who are previously untreated will be enrolled in this study.
2. Male participants:

A male participant must agree to use a contraception during the treatment period and for at least 95 days after the last dose of study treatment and refrain from donating sperm during this period.
3. Female participants:

A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
8. Have adequate organ function. Specimens must be collected within 10 days prior to the start of study intervention.

Exclusion Criteria

\[Participants are excluded from the study if any of the following criteria apply\]

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
4. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
19. Has had an allogenic tissue/solid organ transplant.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Haiquan Chen

Chief, Department of Thoracic Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Haiquan Chen, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

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Fudan University Cancer Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Haiquan Chen, M.D., Ph.D.

Role: CONTACT

(86)13601973588

Bin Li, M.D.

Role: CONTACT

(86)18017319295

Facility Contacts

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Chen Haiquan, MD

Role: primary

+86-21 64175590 ext. 1707

Bin Li, MD

Role: primary

08618017317295

Other Identifiers

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OTSP60942

Identifier Type: -

Identifier Source: org_study_id

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