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Esophageal Cancer, Stage IIPhase 2PERFECTNCT03087864

PDL-1 Targeting in Resectable Oesophageal Cancer

A Phase 2 study testing Atezolizumab, Carboplatin and Paclitaxel in people with Esophageal Cancer, Stage II and Esophageal Cancer Stage III, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Objectives The primary objective of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Carboplatin and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteNetherlands
Study dates
28 Jun 2017to 1 Jul 2019
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven adenocarcinoma of the esophagus or gastro esophageal junction.
  • Surgical resectable (<T4b, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled.
  • T1N+ tumors are eligible.
  • Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.
  • If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction.
  • Age ≥ 18.
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  • ECOG performance status 0 or 1 (cf. Appendix A).
  • Adequate hematological, renal and hepatic functions defined as:
  • neutrophiles ≥ 1.5 x 109/L
  • platelets ≥ 100 x 109/L
  • hemoglobin ≥ 5.6 mmol
  • total bilirubin ≤ 1.5 x upper normal limit
  • creatinine clearance (Cockroft) > 60 ml/min
  • Written, voluntary informed consent
  • Patients must be accessible to follow up and management in the treatment center

Who cannot join

  • Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer.
  • Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
  • T1N0 tumors or in situ carcinoma.
  • Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
  • Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
  • Previous chemotherapy, radiotherapy, and/or treatment with checkpoint inhibitors.
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  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.
  • Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.
  • Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.
  • Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
  • Dementia or altered mental status that would prohibit the understanding and giving of informed consent
  • Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for patients with a history of autoimmune-related hypothyroidism, insulin for patients with type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo with dermatological manifestations only are eligible to enter the study.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.
  • Patients with prior allogeneic stem cell or solid organ transplantation.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Academic Medical Center, Medical Oncology

    Amsterdam, 1100 DD

Other trials in Netherlands

About this study

Official title: PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation.

Objectives The primary objective of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab.

Read the detailed description

Objectives The primary objective of the study of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab.

Secondary objectives are:

  • To assess toxicities of atezolizumab alone and in combination with chemoradiation.
  • To assess completion of chemotherapy and radiation treatment
  • To assess withdrawal rate from surgery
  • To assess post-operative complications.
  • To assess pathological response.
  • To assess R0 resection rate.
  • To assess the relation between gut microbiota composition and response.
  • To assess the relation between gut microbiota composition and toxicity.

Explorative objectives are:

To perform exploratory biomarker analyses from tumor tissue and blood-derived samples and correlate with safety and clinical outcome. Biomarker analyses include (but are not limited to):

  • Expression of PD-1, PD-L1 and FOXP3, presence of tumor infiltrating CD8+/CD4+ cytotoxic/helper T lymphocytes, IFNγ expression, presence of tumor macrophages, STAT3 and STAT6 expression, MHC classI, MHC class II, EBV and MSI status on tumor tissue.
  • RNA sequencing and whole exome sequencing to develop a predictive profile for response to treatment.
  • Analysis of ctDNA extracted from plasma of patients at four time points (baseline, directly after chemoradiation, at surgery and 3 months after surgery) and analyzed using Ion Torrent Next Generation sequence technology as a non-invasive marker for response to treatment.
  • Analysis of peripheral blood mononuclear cells (PBMCs) extracted from whole blood of patients at three time points ((baseline, directly after chemoradiation, at surgery) )
  • Duodenal biopsy and morning faeces sample analysis as predictor of response will be done by HIT Chip flora mapping, an established sensitive RT-qPCR method which is developed for exact and sensitive enumeration of bacterial population.
Being tested
Atezolizumab, Carboplatin, Paclitaxel, Radiotherapy 23 x 1.8 Gy
Keywords
esophageal cancer, PD-L1 inhibition, chemoradiation
Medical subject headings
Esophageal Neoplasms

What participants receive

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

Study groups in NCT03087864
Study groupRoleWhat they receive
Atezolizumab and ChemoradiationExperimentalAtezolizumab 1200 mg i.v. day 1-22-43-64-85 Carboplatin AUC = 2 i.v day 1-8-15-22-29 Paclitaxel 50 mg/m2 i.v day 1-8-15-22-29 Radiotherapy 23 x 1.8 Gy
Receives: Drug: Atezolizumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiotherapy 23 x 1.8 Gy

What is being measured

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

  1. feasibility defined as percentage completion of treatment with atezolizumab.

    The primary endpoint is feasibility defined as percentage completion of treatment with atezolizumab

    Measured: up to 3 months

Secondary outcomes (9)

  1. Incidence and severity of toxicity

    Incidence and severity of toxicity defined to CTCAE v4.03 and Radiation Oncology Group (RTOG) criteria.

    Measured: up to 3 months

  2. Percentage completion of chemotherapy and radiation treatment

    Percentage completion of chemotherapy and radiation treatment

    Measured: up to 3 months

  3. Percentage withdrawal rate from surgery due to atezolizumab related complications

    Percentage withdrawal rate from surgery due to atezolizumab related complications

    Measured: up to 3 months

  4. Percentage delay of surgery due to atezolizumab related complications

    Percentage delay of surgery due to atezolizumab related complications

    Measured: up to 3 months

  5. Incidence and severity of post-operative complications to the Dindo classification

    Incidence and severity of post-operative complications to the Dindo classification

    Measured: up to 3 months

  6. Pathological response according to the Mandard criteria

    Pathological response according to the Mandard criteria

    Measured: up to 3 months

  7. R0 resection rate.

    R0 resection rate.

    Measured: up to 3 months

  8. Progression free survival

    Progression free survival

    Measured: up to 3 months

  9. Overall survival

    Overall survival

    Measured: up to 3 months

Timeline

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

  1. First posted23 Mar 2017
  2. Study start28 Jun 2017
  3. Primary completion1 Jul 2019
  4. Study completion1 Jul 2019

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03087864
Sponsor's protocol ID
2016_325
Acronym
PERFECT
Status last verified
May 2020
First submitted
14 Mar 2017
Last updated
11 May 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • van den Ende T, Ezdoglian A, Baas LM, Bakker J, Lougheed SM, Harrasser M, Waasdorp C, van Berge Henegouwen MI, Hulshof MCCM, Haj Mohammad N, van Hillegersberg R, Mook S, van der Laken CJ, van Grieken NCT, Derks S, Bijlsma MF, van Laarhoven HWM, de Gruijl TD. Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition. Oncoimmunology. 2023 Jul 17;12(1):2233403. doi: 10.1080/2162402X.2023.2233403. eCollection 2023.

    PubMed 37470057

  • van den Ende T, Menting SP, Ambarus CA, van Oijen MGH, van Laarhoven HWM. Cutaneous Toxicity After Chemoradiotherapy and PD-L1 Inhibition in Two Patients with Esophageal Adenocarcinoma: More than Meets the Eye. Oncologist. 2019 Apr;24(4):e149-e153. doi: 10.1634/theoncologist.2018-0674. Epub 2019 Mar 22.

    PubMed 30902915

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Carboplatin and Paclitaxel in people with Esophageal Cancer, Stage II and Esophageal Cancer Stage III, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.

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 15 inclusion and 17 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: finished, as of the sponsor's last update on 11 May 2020. 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 Netherlands. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

feasibility defined as percentage completion of treatment with atezolizumab. (time frame: up to 3 months). 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 NCT03087864, which also lists 2 linked publications.

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 11 May 2020.

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