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Esophageal Squamous Cell CarcinomaPhase 2NCT04084158

A Study of Toripalimab Combined With Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

A Phase 2 study testing Toripalimab injection (JS001), Paclitaxel, Albumin-Bound and Radiotherapy in people with Esophageal Squamous Cell Carcinoma, run by Zhejiang Cancer Hospital at 1 site in China.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

The purpose of this study is to explore the efficacy and safety of Toripalimab injection (JS001) given before and after concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. 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?
Toripalimab injection (JS001), Paclitaxel, Albumin-Bound and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteChina
Study dates
7 Sep 2019to 30 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 18≤age≤75.
  • Histologically or cytologically confirmed esophageal squamous carcinoma.
  • Patients must have unresectable disease as assessed by thoracic surgeons or refuse surgical treatment.
  • The investigator confirmed at least one measurable lesion according to RECIST 1.1.
  • Stage II-IVA (AJCC 8th)
  • No adjacent organs infringed confirmed by endoscopic ultrasonography (T1-3).
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  • ECOG PS 0-1.
  • FEV1>0.8L
  • Life expectancy is not less than 12 weeks.
  • No prior chemotherapy, radiotherapy, biotherapy, immunotherapy or other anti-tumor treatment for esophageal cancer.
  • Adequate organ function defined at baseline as: 1) ANC ≥1.5×109 /L，PLt ≥100×109 /L，Hb ≥90 g/L; 2) TBIL ≤1.5×ULN, ALT ≤2.5ULN, AST ≤2.5ULN, BUN and Cr ≤1×ULN or Ccr ≥50ml/min (Cockcroft-Gault formula); 3) INR ≤1.5×ULN or PT ≤1.5×ULN (If the patient is receiving anticoagulant therapy, PT should be within the intended use range of the anticoagulant drug); 4) Myocardial zymogram is within normal range.
  • Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative. Besides, subjects should agree to use effective methods of contraception during the trial and within 2 months of the last dose of anti-PD-1 antibody. For male subjects whose spouse are of childbearing age, effective contraceptive methods should be used during the trial and within 2 months after the last dose of anti-PD-1 antibodies;
  • Subject volunteers to join the study, Signs informed consent, has good compliance and can cooperate with follow-up.

Who cannot join

  • Those with prior or concurrent uncured malignant tumor. cured skin basal cell carcinoma, cervical cancer and superficial bladder cancer were excluded.
  • Esophageal cancer patients with primary multifocal lesions.
  • Those with the pathology of small cell esophageal carcinoma, esophageal adenocarcinoma or mixed carcinoma.
  • Primary esophageal squamous carcinoma with active hemorrhage of the primary lesion within 2 months.
  • Those with primary esophageal lesion that was closely related to tracheal bronchus and great vessels, and were evaluated with a great risk of perforation and massive bleeding by the researchers.
  • Patients with any active autoimmune disease or autoimmune disease history (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, and hypothyroidism (those with normal thyroid function after hormone replacement therapy could be enrolled); those with leucoderma or childhood asthma that was completely relieved and required no intervention during adulthood could be enrolled, while asthma patients requiring bronchodilators and medical intervention should not be enrolled.
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  • Patients with uncontrolled cardiovascular disease: grade II and above myocardial ischemia or myocardial infarction, and poorly-controlled arrhythmia (including the QTc interval of ≥470 ms); those with grade III-IV cardiac insufficiency according to the NYHA criteria, or those whose echocardiography revealed left ventricular ejection fraction (LVEF) of <50%; and those having myocardial infarction within 1 year.
  • Those with active infection or fever of >38.5 ℃ with unknown cause during the screening period and before the first administration (patients with tumor-induced fever judged by the researchers could be enrolled).
  • Those with interstitial lung disease or active non-infectious pneumonia history or evidence.
  • Those with congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B (HBV-DNA≥104 copies/ml) or hepatitis C (positive hepatitis C antibody, and the HCR-RNA was higher than the lower limit of detection of the analysis method).
  • Those who had previously received other PD-1 antibody treatment or PD-1/PD-L1 targeted immune therapy.
  • Those who were known to be allergic to paclitaxel, carboplatin, macromolecular protein preparation, or any anti-PD-1 antibody component.
  • Subjects who required to use corticosteroids (prednison dose of > 10 mg/day) or other immunosuppressors for systemic treatment within the first 7 days of research. In the absence of active autoimmune disease, glucocorticoids at physiological dose (≤ 10 mg/day prednison or equivalent drug), inhalation or local application of steroid and adrenocortical hormone replacement treatment with prednison at the dose of > 10 mg/day.
  • Those receiving anti-tumor monoclonal antibody (mAb) and targeted small molecule treatment within 4 weeks before the initial use of the research drug, or those with unrecovered adverse events induced by the previous treatment (namely, grade ≤ 1 or reaching the baseline level). Apart from subjects with ≤ grade 2 nervous lesion or ≤ grade 2 alopecia, any subject that had received major surgery should sufficiently recover from the toxic reaction and/or complication resulted from the surgical intervention before the initiation of treatment.
  • Those who were within 4 weeks before the initial use of the research drug (subjects that had entered the follow-up period were calculated at the final use of experimental drug or instrument) or those who were participating other clinical research.
  • Patients should be inoculated with live vaccine within 4 weeks before the initial use of research drug, inactivated viral vaccine specific to seasonal influenza for injection was allowed, but the nasal use of live attenuated influenza vaccine was not allowed.
  • Pregnant women or breast-feeding women.
  • Subjects who had other factors that might force them to terminate the research ahead of time, such as the development of other severe disease (including mental disease) that required combined treatment, seriously abnormal laboratory examination value, and family or social factors that might affect the subject safety or experimental data collection, as judged by the researchers.
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Trial locations and contacts

1 site in 1 country.

China1 site

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310022

Other trials in China

About this study

Official title: A Phase II, Randomized, Open Label, Multi-center Design Study of Toripalimab Given Before and After Concurrent Chemoradiotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

The purpose of this study is to explore the efficacy and safety of Toripalimab injection (JS001) given before and after concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

Read the detailed description

This was a randomized, open label and multi-center phase II clinical study, which aimed to evaluate the efficacy and safety of Toripalimab injection (JS001) induction immunotherapy, plus concurrent chemoradiation, and successive Toripalimab injection (JS001) maintenance immunotherapy relative to those of standardized concurrent chemoradiation for locally advanced esophageal squamous carcinoma patients that could not receive surgical treatment or refuse surgery. All patients conforming to the inclusion and exclusion criteria were assigned as the experimental arm and control arm at the ratio of 1:1 through the stratified block randomization method. Prior to concurrent chemoradiation, the experimental arm was given anti-PD-1 antibody Toripalimab injection (JS001) for 2 cycles, concurrent chemoradiation was initiated within 4 weeks after the induction immunotherapy, then patients were evaluated within 4 weeks after the completion of concurrent chemoradiation. Those who had not achieved PD were given 2 cycles of consolidation chemotherapy, and Toripalimab injection (JS001) was continued to at most 1 year or to identified disease progression, intolerable toxicity, or the subjects asked to withdraw initiatively, or researchers judged that the subjects should withdraw from the study. The control arm was given concurrent chemoradiation alone, with sequential consolidation chemotherapy for 2 cycles. The primary endpoint is progression-free survival (PFS), Secondary end points include objective response rate (ORR), overall survival (OS), duration of response (DoR), time to distant metastasis (TTDM).

Being tested
Toripalimab injection (JS001), Paclitaxel, Albumin-Bound, Radiotherapy, Platinum-Based Drug
Keywords
Esophageal Squamous Cell Carcinoma, PD-1 antibody
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.

  • Toripalimab injection (JS001)Drug

    Toripalimab injection (JS001) is a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies.

  • Paclitaxel, Albumin-BoundDrug

    Paclitaxel

  • RadiotherapyRadiation

    PTV 50.4Gy/28 fractions, PGTV 61.6Gy/28 fractions, once a day, 5 days a week.

  • Platinum-Based DrugDrug

    carboplatin

Study groups in NCT04084158
Study groupRoleWhat they receive
Toripalimab+chemoradiationExperimentalInduction immunotherapy: Toripalimab injection (JS001) 3mg/kg IV q 14 days x 2 cycles. Concurrent Chemoradiotherapy: Starting within 4 weeks after the first cycle induction immunotherapy. carboplatin AUC = 2 + albumin-bound paclitaxel 60 mg/m2 or paclitaxel liposome 45 mg/m2 or paclitaxel 45 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 50.4 Gy given in 1.8 Gy fractions daily x 28 fractions. Progression of disease (PD): The progress of the disease will be assessed within 4 weeks after concurrent chemoradiotherapy. Patients without disease progression continue to receive consolidation and adjuvant therapy. Consolidation chemotherapy: carboplatin AUC = 6 + albumin-bound paclitaxel 260 mg/m2 or paclitaxel liposome 135 mg/m2 or paclitaxel 135 mg/m2 IV q 21 days x 6 cycles. Adjuvant immunotherapy:Toripalimab injection (JS001) 3mg/kg IV q 14 days up to 1 year.
Receives: Drug: Toripalimab injection (JS001); Drug: Paclitaxel, Albumin-Bound; Radiation: Radiotherapy; Drug: Platinum-Based Drug
chemoradiationActive comparatorConcurrent Chemoradiotherapy: carboplatin AUC = 2 + albumin-bound paclitaxel 60 mg/m2 or Liposome paclitaxel 45 mg/m2 or paclitaxel 45 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 50.4 Gy given in 1.8 Gy fractions daily x 28 fractions. Progression of disease (PD): The progress of the disease will be assessed within 4 weeks after concurrent chemoradiotherapy. Patients without disease progression continue to receive consolidation therapy. Consolidation chemotherapy: carboplatin AUC = 6 + albumin-bound paclitaxel 260 mg/m2 or paclitaxel liposome 135 mg/m2 or paclitaxel 135 mg/m2 IV q 21 days x 6 cycles.
Receives: Drug: Paclitaxel, Albumin-Bound; Radiation: Radiotherapy; Drug: Platinum-Based Drug

What is being measured

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

  1. PFS

    Progression-Free Survival

    Measured: 2 years

Secondary outcomes (4)

  1. Objective Response Rate

    Ratio of CR and PR (RECIST 1.1) in all subjects

    Measured: analysis is completed 4 weeks after concurrent chemoradiation

  2. OS

    Overall Survival

    Measured: 3 years

  3. DoR

    Duration of Response

    Measured: 2 years

  4. TTDM

    Time to distant Metastasis

    Measured: 3 years

Timeline

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

  1. First posted10 Sep 2019
  2. Study start7 Sep 2019
  3. Primary completion30 Dec 2021 (estimated)
  4. Study completion30 Dec 2021 (estimated)

Why it stopped: combination arm delevelped significant poor prognosis

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04084158
Sponsor's protocol ID
IESO001
Status last verified
Feb 2021
First submitted
5 Sep 2019
Last updated
23 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Toripalimab injection (JS001), Paclitaxel, Albumin-Bound and Radiotherapy in people with Esophageal Squamous Cell Carcinoma, run by Zhejiang Cancer 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 13 inclusion and 19 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: paused, as of the sponsor's last update on 23 Feb 2021. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS (time frame: 2 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 NCT04084158.

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 23 Feb 2021.

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