Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05281003
Other study ID # OTSP60942
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date February 20, 2023
Est. completion date September 1, 2026

Study information

Verified date July 2023
Source Fudan University
Contact Haiquan Chen, M.D., Ph.D.
Phone (86)13601973588
Email Hqchen1@yahoo.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 128
Est. completion date September 1, 2026
Est. primary completion date September 1, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
China Fudan University Cancer Center Shanghai Shanghai
China Fudan University Shanghai Cancer Center Shanghai Shanghai

Sponsors (2)

Lead Sponsor Collaborator
Fudan University Merck Sharp & Dohme LLC

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Other Spatial proteomic measurement of hypoxia and defined cell lineages in baseline or post-treatment tumor samples from all eligible participants with locally advanced ESCC Spatial proteomic measurement of hypoxia and defined cell lineages are assessed by multiplex IHC assay. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Other Single cell genomic measurement of hypoxia pathway genes in post-treatment tumor samples from all eligible participants with locally advanced ESCC. Single cell genomic measurement of hypoxia pathway genes are assessed by single cell RNA sequencing. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Other PCR rate in eligible participants with locally advanced ESCC whose tumors are PD-L1 biomarker positive (CPS =10) PCR is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by CPS scoring methods. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Other R0 resection rate in all eligible participants with locally advanced ESCC R0 resection is defined as microscopically margin-negative resection, without remaining gross or microscopic tumor in the primary tumor bed. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Other EFS in eligible participants with locally advanced ESCC, stratified by PD-L1 biomarker expression (CPS =10, =1 and <1) EFS is defined as time from allocation to any of the following events: progression of disease that precludes surgery, local or distant recurrence, a second primary tumor, or death due to any cause. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by CPS scoring methods. Up to approximately 48 months (1-September-2022 till 1-September-2026)
Primary Pathologic complete response (pCR) rate in all eligible participants with locally advanced ESCC Pathologic complete response is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node. Up to approximately 6 months (1-September-2022 till 1-March-2023)
Primary Major hypoxia signals in baseline or post-treatment tumor samples from all eligible participants with locally advanced ESCC Major hypoxia signals in tumor microenvironment (TME) are assessed by IHC methods, using tumor samples acquired pre- and post-treatment. Major hypoxia signals are to be compared between non-responders and responders to pembrolizumab plus SOC chemotherapy. In this neoadjuvant study, we define that patients who fail to reach major pathologic response (mPR) before surgery are classified as non-responders, and patients who reach mPR before surgery as responders. MPR is assessed by the Mandard TRG. MPR is defined as combined TRG1 and TRG2. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Secondary PCR rate in eligible participants with locally advanced ESCC whose tumors are PD-L1 biomarker positive (CPS =1) Pathologic complete response is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by combined positive score (CPS) scoring methods. Up to approximately 12 months (1-September-2022 till 1-September-2023)
Secondary Event-free survival (EFS) in the 3-year follow-up of all eligible participants with locally advanced ESCC EFS is defined as time from allocation to any of the following events: progression of disease that precludes surgery, local or distant recurrence, a second primary tumor, or death due to any cause. Up to approximately 48 months (1-September-2022 till 1-September-2026)
Secondary Cell lineage-specific hypoxia signals in baseline or post-treatment tumor samples from all eligible participants with locally advanced ESCC Lineage-specific hypoxia signals in TME are assessed by multi-color flow cytometry in defined immune subsets and tumor, using surgical tumor samples acquired post-treatment. Lineage-specific hypoxia signals are to be compared between non-responders and responders to pembrolizumab plus SOC chemotherapy. In this neoadjuvant study, we define that patients who fail to reach mPR before surgery are classified as non-responders, and patients who reach mPR before surgery as responders. MPR is assessed by the Mandard TRG. MPR is defined as combined TRG1 and TRG2. Up to approximately 12 months (1-September-2022 till 1-September-2023)
See also
  Status Clinical Trial Phase
Recruiting NCT06056336 - Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma Phase 2
Suspended NCT04084158 - A Study of Toripalimab Combined With Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma. Phase 2
Active, not recruiting NCT04242199 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors Phase 1
Not yet recruiting NCT05561699 - Sequential Preoperative Penpulimab Combined With Chemoradiotherapy(CRT) for Locally Advanced Esophageal Squamous Cell Cancer N/A
Active, not recruiting NCT04543617 - A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy Phase 3
Recruiting NCT06190782 - Local Therapy for Oligometastatic ESCC Patients Treated With PD-1 Inhibitor Phase 3
Completed NCT05557955 - Identification of Breath Biomarkers in Esophageal Cancer
Recruiting NCT04045496 - A First-in-Human, Phase 1 Study of JAB-3312 in Adult Patients With Advanced Solid Tumors Phase 1
Recruiting NCT04584008 - Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics N/A
Not yet recruiting NCT03766178 - Study of Anti-PD-1 Antibody SHR-1210 Plus Nimotuzumab in the Treatment of Advanced Esophageal Squamous Cell Carcinoma Phase 2
Recruiting NCT02913066 - S-1 IMRT Versus S-1 and Cisplatin Concurrent IMRT in Inoperable Esophageal Squamous Cell Carcinoma Phase 2
Completed NCT02399306 - Chemoradiotherapy With or Without Enteral Nutrition for Locally Advanced Thoracic Esophageal Carcinoma Phase 3
Completed NCT01605305 - Study on FOLFOX6 as First-line Therapy to Treat Recurrent or Metastatic Esophageal Cancer Phase 2
Not yet recruiting NCT05552651 - Envafolimab Combined With Chemotherapy in Neoadjuvant Therapy for Resectable Esophageal Squamous Cell Carcinoma Phase 2
Recruiting NCT05520619 - Combination of Tislelizumab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-002) Phase 2
Terminated NCT03251417 - Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma Phase 2
Recruiting NCT05990231 - Cadonilimab/Anlotinib in Locally Advanced or Relapsed/Metastatic ESCC Patients After Failure of PD-1 Combined With Platinum-containing Chemotherapy Phase 2
Recruiting NCT04644250 - Combination of Toripalimab and Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma Phase 2
Completed NCT02916511 - Study of Extensive Clinical Target Volumes in Postoperative Radiotherapy Concurrent With Chemotherapy for Esophageal Squamous Cell Carcinoma Phase 2
Terminated NCT04032704 - A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors Phase 2