Immunotherapy in Combination With Chemoradiotherapy in Unresectable Locally Advanced Esophageal Cancer

NCT ID: NCT06173986

Last Updated: 2023-12-18

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

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-10

Study Completion Date

2027-12-30

Brief Summary

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SCR-ESCC-02 is a multicenter, phase I/II clinical study to investigate the safety and efficacy of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 therapy in patients diagnosed with locally advanced, unresectable esophageal cancer.

Detailed Description

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Immunotherapy has shown promising results in advanced esophageal cancer, but its optimal integration into the management of unresectable locally advanced disease remains uncertain. The significant tumor regression and reduced tumor residual achieved through immunochemotherapy offer an opportunity to enhance the effectiveness of subsequent radiotherapy. This phase I/II clinical study aims to investigate the efficacy and safety of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 for patients with unresectable locally advanced esophageal cancer. The study's co-primary endpoints are progression-free survival (PFS) and treatment completion rate.

Conditions

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Esophageal Squamous Cell Carcinoma Unresectable Locally Advanced Esophageal Cancer

Keywords

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Immunotherapy Induction immunochemotherapy Concurrent Immuno-Chemoradiotherapy Unresectable locally advanced esophageal cancer Esophageal Squamous Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IC+ICRT group

2 cycles of PD-1 inhibitor + nab-paclitaxel + cisplatin followed by concurrent PD-1 inhibitor + radiotherapy (45-50Gy/25fx) + nab-paclitaxel + cisplatin

Group Type EXPERIMENTAL

PD-1inhibitor

Intervention Type DRUG

PD-1 inhibitor, Q3W, until disease progression or unacceptable toxicity or treatment reaches 1 year

nab-paclitaxel + cisplatin

Intervention Type DRUG

Induction phase: nab-paclitaxel + cisplatin, Q3W × 2 cycles; Concurrent ICRT phase: nab-paclitaxel + cisplatin, QW × 5 cycles

Radiotherapy

Intervention Type RADIATION

Primary tumor and metastatic lymph nodes, DT:45-50Gy/25fx, starting within 4 weeks following the completion of the last induction immunochemotherapy cycle

Interventions

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PD-1inhibitor

PD-1 inhibitor, Q3W, until disease progression or unacceptable toxicity or treatment reaches 1 year

Intervention Type DRUG

nab-paclitaxel + cisplatin

Induction phase: nab-paclitaxel + cisplatin, Q3W × 2 cycles; Concurrent ICRT phase: nab-paclitaxel + cisplatin, QW × 5 cycles

Intervention Type DRUG

Radiotherapy

Primary tumor and metastatic lymph nodes, DT:45-50Gy/25fx, starting within 4 weeks following the completion of the last induction immunochemotherapy cycle

Intervention Type RADIATION

Other Intervention Names

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Immunotherapy Chemotherapy

Eligibility Criteria

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Inclusion Criteria

1. Age between 18 and 75 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
3. Clinical stage meeting the criteria of T1N+M0 or T2-4aN0-3M0 based on the 8th UICC-TNM classification.
4. Ineligibility for surgical resections due to patients' unwillingness for surgery, technically unresectable disease, or being medically unfit for surgery.
5. No prior anti-tumor treatment, including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy.
6. Adequate hematological, pulmonary, cardiac, hepatic, renal, and thyroid function.
7. Willingness to use contraception with an adequate method throughout the study.
8. Documented informed consent.

Exclusion Criteria

1. History of malignant disease within the 5 years preceding enrollment or presence of other malignant tumors or non-squamous cell carcinoma components.
2. High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation as determined by the investigators.
3. Weight loss exceeding 20% within the 90 days prior to the first day of drug administration.
4. Presence of long-standing unhealed wounds or fractures or undergoing major surgical resections within 60 days preceding the first day of drug administration.
5. Presence of any severe or uncontrolled coexisting diseases, including but not limited to:

* Uncontrolled hypertension
* History of interstitial lung disease or non-infectious pneumonia
* Active hepatitis B or C, syphilis, or other active and uncontrolled infections
* Cardiac insufficiency (NYHA≥2)
* Renal dysfunction requiring dialysis
* Active autoimmune disease
* History of acquired or congenital immunodeficiency diseases
6. Occurrence of serious arterial/venous thrombotic events within 6 months prior to the first day of drug administration.
7. History of psychotropic substance abuse or inability to quit, or patients with psychotic disorders.
8. Allergy to study drugs.
9. Patients deemed unsuitable for participation due to severe comorbidities or other reasons determined by the investigators.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Chest Hospital

OTHER

Sponsor Role lead

Responsible Party

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Wen Yu

Vice Director of Radiation Oncology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wen Yu, M.D

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital

Locations

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Shanghai Chest Hospital

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wen Yu, M.D

Role: CONTACT

Phone: 021-22200000-3203

Email: [email protected]

Facility Contacts

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Wen Yu, M.D

Role: primary

References

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Hulshof MCCM, Geijsen ED, Rozema T, Oppedijk V, Buijsen J, Neelis KJ, Nuyttens JJME, van der Sangen MJC, Jeene PM, Reinders JG, van Berge Henegouwen MI, Thano A, van Hooft JE, van Laarhoven HWM, van der Gaast A. Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study). J Clin Oncol. 2021 Sep 1;39(25):2816-2824. doi: 10.1200/JCO.20.03697. Epub 2021 Jun 8.

Reference Type BACKGROUND
PMID: 34101496 (View on PubMed)

Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

Reference Type BACKGROUND
PMID: 34454674 (View on PubMed)

Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.

Reference Type BACKGROUND
PMID: 33373868 (View on PubMed)

Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.

Reference Type BACKGROUND
PMID: 36990609 (View on PubMed)

Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 2021 Apr;17(10):1143-1153. doi: 10.2217/fon-2020-0969. Epub 2021 Feb 3.

Reference Type BACKGROUND
PMID: 33533655 (View on PubMed)

Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16.

Reference Type BACKGROUND
PMID: 34269067 (View on PubMed)

Wang Z, Shao C, Wang Y, Duan H, Pan M, Zhao J, Wang J, Ma Z, Li X, Yan X. Efficacy and safety of neoadjuvant immunotherapy in surgically resectable esophageal cancer: A systematic review and meta-analysis. Int J Surg. 2022 Aug;104:106767. doi: 10.1016/j.ijsu.2022.106767. Epub 2022 Jul 14.

Reference Type BACKGROUND
PMID: 35840049 (View on PubMed)

Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.

Reference Type BACKGROUND
PMID: 35108059 (View on PubMed)

Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lievre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125.

Reference Type BACKGROUND
PMID: 33789008 (View on PubMed)

Other Identifiers

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SCR-ESCC-02

Identifier Type: -

Identifier Source: org_study_id