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Esophageal Squamous Cell CarcinomaPhase 1/2NCT03278626

Immune Checkpoint Therapy With Nivolumab Esophageal Squamous Cell Carcinoma

A Phase 1/2 study testing Nivolimumab+Carboplatin/paclitaxel+Radiation in people with Esophageal Squamous Cell Carcinoma, run by NYU Langone Health at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and carboplatin using a schedule and doses identical to those used in the CROSS trial. Following a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Squamous Cell Carcinoma
What is being tested?
Nivolimumab+Carboplatin/paclitaxel+Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
5 sitesUnited States
Study dates
27 Jun 2017to 31 May 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed, treatment-naive esophageal squamous cell carcinoma
  • Previously obtained archival tumor tissue, or tissue obtained by endoscopically guided core biopsy at screening
  • TanyN1-3 or T3-4 N0as determined by EUS and PET/CT. All palpable or CT/PET visible lymph nodes outside the usual surgical field must be biopsy-proven negative for cancer.
  • All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible. Endoscopy reports or subsequent GI clinic note should clearly state both the T and N stage.
  • All patients must have initial PET/CT scans to document no evidence of metastatic or unresectable squamous cell cancer
  • All patients with tumors involving the thoracic esophagus must undergo bronchoscopy to document the absence of a fistula No known contraindication to the use of taxanes or platinum compounds.
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  • No history of severe hypersensitivity reaction to Cremophor® EL.
  • Patients who are ≥ 18 years old are eligible for this study. Neither specific gender distribution, nor specific racial or ethnic origins are necessary for enrollment in this study.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • A patient must be capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject's behalf
  • Deemed a suitable candidate for esophagectomy by the treating surgeon as documented in a pre-operative assessment visit per standard practice at each participating institution.
  • Deemed a suitable candidate for radiation therapy by the treating radiation oncologist as documented in a standard pretreatment visit per standard practice at each participating institution.
  • Patient must be non-pregnant and non-nursing. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to C1D1.
  • Screening Laboratory Values must meet the following criteria and should be obtained within 14 days prior to C1D1 (see Table 1 below)
  • Patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement; Patients with HBV core positive, must have negative viral load measurements
  • Screening Laboratory Values must meet the following criteria and should be obtained within 14 days prior to randomization/registration (see Table 1 below) Test Acceptable Result WBC ≥ 2000/µL Neutrophils ≥ 1500/µL Platelets ≥ 100,000 /µL Hemoglobin > 9.0 g/dL Serum Creatinine ≤ 1.5 x ULN OR Creatinine Clearance (CrCl)* ≥ 40 mL/min AST ≤ 3 x ULN ALT ≤ 3 x ULN Total Bilirubin** ≤ 1.5 x ULN
  • Oxygen Saturation (O2 Sat.) ≥92% on ambient air Hepatitis B status HBV Surface Antigen Negative HBV Surface Antibody Positive or Negative HBV Core Antibody Negative Hepatitis C status Anti-HCV Total Antibody Negative HCV RNA analysis Negative HIV status Rapid HIV 1/2 Antibodies Negative Creatinine Clearance Calculated using the Cockcroft-Gault formula
  • Female CrCl = (140- age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
  • Male CrCl = (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
  • Total Bilirubin ≤ 1.5 x ULN, except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL

Who cannot join

  • T1-2 N0 as determined by EUS and PET/CT.
  • Pregnant or lactating women
  • Active or prior documented autoimmune or inflammatory disorders including but not limited to inflammatory bowel disease; systemic lupus erythematosus; type I diabetes mellitus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
  • Subjects with vitiligo or alopecia
  • Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
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  • The use of immunosuppressive medication within 28 days prior to the first dose of nivolumab. The following are exceptions to this criterion:
  • Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g. intra-articular injection)
  • Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication
  • Positive test for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Active Hepatitis B or Hepatitis C (defined as positive-HBV surface antigen or detectable HCV-antibody) indicating acute or chronic infection. Patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement.
  • Prior treatment with any immunotherapy
  • Any other factors, including psychiatric or social, that in the opinion of the treating physician makes the patient an inappropriate candidate for a study.
  • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no ESCC Nivolumab requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • As there is potential for hepatic toxicity with nivolumab or nivolumab non-drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  • Patients with a history of allergy to the study drug components are excluded.
  • No herbal supplements are allowed in this protocol.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Califonia, San Diego

    La Jolla, California, 92093

  • University of Southern California

    Los Angeles, California, 90033

  • New York University School of Medicine

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Oregon Health Sciences University

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase I/II Open Label Multi Center Study of Immune Checkpoint Therapy With Nivolumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and carboplatin using a schedule and doses identical to those used in the CROSS trial. Following a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care established by the CROSS trial: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation will be administered with chemotherapy at 1.8 Gy/fraction × 28 fractions to a total dose of 50.4 Gy, the standard radiation dose administered in the United States for trimodality therapy that includes concurrent therapy with carboplatin and paclitaxel. A decrease in dose to 41.4 Gy per the protocol established by van Hagen, et al. will be permitted before discontinuing therapy due to unacceptable toxicity. While the CROSS study administered only 5 weekly doses of chemotherapy during the 5 weeks of radiation, the higher dose of 50.4 Gy (1.8 Gy/fraction ×28 fractions over 5½ weeks) utilized in this study permits for a sixth dose during the additional week of radiation.

Being tested
Nivolimumab+Carboplatin/paclitaxel+Radiation
Keywords
Locally Advanced Esophageal Squamous Cell Carcinoma
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.

  • Nivolimumab+Carboplatin/paclitaxel+RadiationDrug

    Also called Opdivo, Paraplatin, Taxol

    In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).

Study groups in NCT03278626
Study groupRoleWhat they receive
Nivolimumab+Carboplatin/paclitaxel+RadiationOther240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation
Receives: Drug: Nivolimumab+Carboplatin/paclitaxel+Radiation

What is being measured

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

  1. Phase 1: Number of Unacceptable Toxicity (UT) Events

    UT is defined as:

    1. Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)
    2. any toxicity that results in a > 2-week delay in chemoradiation

    Measured: 92 days (up to 28 days after Day 64)

  2. Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)

    Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue

    Measured: 5-8 Weeks post radiation treatment (7-8 months after treatment start)

Timeline

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

  1. First posted11 Sep 2017
  2. Study start27 Jun 2017
  3. Primary completion7 Nov 2019
  4. Study completion31 May 2021

Why it stopped: The study was stopped earlier than anticipated due to slow accrual

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03278626
Sponsor's protocol ID
16-00971
Status last verified
Mar 2022
First submitted
31 Aug 2017
Last updated
28 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolimumab+Carboplatin/paclitaxel+Radiation in people with Esophageal Squamous Cell Carcinoma, run by NYU Langone Health at 5 sites in United States.

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 20 inclusion and 20 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: stopped early, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 28 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase 1: Number of Unacceptable Toxicity (UT) Events (time frame: 92 days (up to 28 days after Day 64)). The study lists 2 primary outcomes in all. 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 NCT03278626.

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 28 Mar 2022.

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