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Esophageal Squamous Cell CarcinomaPhase 3KEYSTONE-002NCT04807673

Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002)

A Phase 3 study testing Pembrolizumab, Paclitaxel and Cisplatin in people with Esophageal Squamous Cell Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Esophageal Squamous Cell Carcinoma
What is being tested?
Pembrolizumab, Paclitaxel and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
342 participants
Where
1 siteChina
Study dates
1 Dec 2021to May 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed esophageal squamous cell carcinoma;
  • R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification);
  • No suspicious metastatic lymph nodes on the clavicle;
  • Have a performance status of 0 or 1 on the ECOG Performance Scale;
  • Age 18-75 years old, both men and women;
  • Be willing and able to provide written informed consent/assent for the trial;
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  • Demonstrate adequate organ function ;
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
  • Be willing to provide tissue, blood, and urine samples. Tissue should be from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) before initiation of treatment on Day 1.
  • Have not received systemic or local treatment for esophageal cancer in the past.

Who cannot join

  • Ineligibility or contraindication for esophagectomy;
  • Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer
  • Active autoimmune disease or history of autoimmune disease;
  • Requiring systemic treatment with either corticosteroids or other immunosuppressive medications;
  • Subjects with a history of symptomatic interstitial lung disease;
  • History of allergy to study drug components;
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  • Women must not be pregnant or breast-feeding;
  • Patient has received prior chemotherapy, radiotherapy, target therapy ，and immune therapy for this malignancy or any other past malignancy;
  • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Hongjing Jiang, MD,PhD contact

18622221069

jianghongjing@tmu.edu.cn

Xiaobin Shang, MD,PhD contact

18622221071

shangxiaobin@tmu.edu.cn

China1 site, 1 recruiting

  • Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

    Hongjing Jiang, MD,PhD, 18622221069, jianghongjing@tmu.edu.cn

    Xiaobin Shang, MD,PhD, 18622221071, shangxiaobin@tmu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: A Multicenter Randomized, Controlled Phase III Clinical Trial of Pembrolizumab Plus Paclitaxel and Cisplatin Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-002)

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter.

Read the detailed description

Preoperative chemoradiotherapy with radical surgery is the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC) in the NCCN guidelines. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter. The primary study hypothesis is that Event Free Survival (EFS) is superior with pembrolizumab plus neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy in participants with ESCC.

Being tested
Pembrolizumab, Paclitaxel, Cisplatin, neoadjuvant chemoradiotherapy
Keywords
esophageal squamous cell carcinoma, Immunotherapy, neoadjuvant therapy
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called Keytruda

    Neoadjuvant period: pembrolizumab 200mg IV D1, Q3W, and preoperative therapy with three cycles.

    Adjuvant period: pembrolizumab 200 mg IV D1, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.

  • PaclitaxelDrug

    Neoadjuvant period: paclitaxel 135mg/m^2 IV on Day 2 Q3W, and a total of three cycles.

  • CisplatinDrug

    Neoadjuvant period: cisplatin 80 mg/m^2 IV on Day 2 Q3W, and a total of three cycles.

  • neoadjuvant chemoradiotherapyRadiation

    neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week

Study groups in NCT04807673
Study groupRoleWhat they receive
Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)ExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year. Surgery: McKeown esophagectomy
Receives: Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Cisplatin
neoadjuvant chemoradiotherapy+ Surgery (114)Experimentalneoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. Surgery: McKeown esophagectomy
Receives: Radiation: neoadjuvant chemoradiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event Free Survival (EFS)

    EFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigator, or recurrence, or metastasis, or death due to any cause, whichever occurs first. For this analysis, EFS will be assessed in participants with ESCC.

    Measured: Up to approximately 2.5 years

Secondary outcomes (9)

  1. Overall Survival (OS)

    OS is defined as the time from randomization to death due to any cause.

    Measured: 3 and 5 years

  2. Disease Free Survival (DFS)

    Percentage of Participants With DFS, as Assessed by RECIST 1.1. DFS is defined as the time from randomization to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.

    Measured: 3 and 5 years

  3. Major pathologic response (MPR)

    MPR is defined as viable tumor comprised ≤ 10% of resected tumor specimens.

    Measured: 1 month after resection

  4. Objective response rate (ORR)

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator. For this analysis, ORR will be assessed in all participants.

    Measured: 1 month after resection

  5. Pathologic Complete Response (PCR)

    PCR is defined as pT0N0M0

    Measured: 1 month after resection

  6. assessment in perioperation

    R0 resection rate， Time of operation， Quantity of bleeding， Thoracic Drainage， Days of Hospitalization， Rate of Operative Complication， Mortality of perioperation

    Measured: perioperative period

  7. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    All participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Event,Version 4.0(CTC AE4.0).

    Measured: up to 16 months

  8. Quality of life differences (EORTC QLQ-C30)

    The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-C30) questionnaire. Patients will be invited to finish the questionnaire at the first day of randomization, before surgery and after surgery (3m, 6m, 12m and 24 months).

    Measured: 2.5 years

  9. Quality of life differences (EORTC QLQ-OES18)

    The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-OES18) questionnaire. Patients will be invited to finish the questionnaire at the first day of randomization, before surgery and after surgery (3m, 6m, 12m and 24 months).

    Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2021
  2. Study start1 Dec 2021
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
342 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04807673
Sponsor's protocol ID
TianjinCIH20210096
Acronym
KEYSTONE-002
Status last verified
May 2022
First submitted
11 Mar 2021
Last updated
1 Jun 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Shang X, Zhang W, Zhao G, Liang F, Zhang C, Yue J, Duan X, Ma Z, Chen C, Pang Q, Zhang W, Liu L, Ren X, Meng B, Zhang P, Ma Y, Zhang L, Li H, Kang X, Li Y, Jiang H. Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002). Front Oncol. 2022 Mar 31;12:831345. doi: 10.3389/fonc.2022.831345. eCollection 2022.

    PubMed 35433421

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Paclitaxel and Cisplatin in people with Esophageal Squamous Cell Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Hongjing Jiang, MD,PhD (18622221069, jianghongjing@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival (EFS) (time frame: Up to approximately 2.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04807673, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.

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