PDL-1 Targeting in Resectable Oesophageal Cancer

NCT03087864 | Completed Phase 2 DMC

• 1 other identifier: 2016_325
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Cancer, Stage II; Esophageal Cancer Stage III

Keywords

esophageal cancer; PD-L1 inhibition; chemoradiation

Outcome Measures

Primary Outcomes (1)

• feasibility defined as percentage completion of treatment with atezolizumab.

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

  up to 3 months

Secondary Outcomes (9)

• Incidence and severity of toxicity

  up to 3 months

• Percentage completion of chemotherapy and radiation treatment

  up to 3 months

• Percentage withdrawal rate from surgery due to atezolizumab related complications

  up to 3 months

• Percentage delay of surgery due to atezolizumab related complications

  up to 3 months

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

  up to 3 months

Other Outcomes (1)

• Potential biomarker development based on assessment of tumour biopsies, blood- and faecal samples and the proposed mechanism of action of study drugs.

  up to 3 months

Study Arms (1)

Atezolizumab and Chemoradiation

EXPERIMENTAL

Atezolizumab 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

Drug: Atezolizumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiotherapy 23 x 1.8 Gy

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg i.v. day 1-22-43-64-85

Atezolizumab and Chemoradiation

Carboplatin DRUG

Chemotherapy

Atezolizumab and Chemoradiation

Paclitaxel DRUG

Chemotherapy

Atezolizumab and Chemoradiation

Radiotherapy 23 x 1.8 Gy RADIATION

Radiotherapy

Atezolizumab and Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• UMC Utrecht: collaborator

Study Sites (1)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 37470057 DERIVED

• 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.

  PMID: 30902915 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

atezolizumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Hanneke WM van Laarhoven, Prof. dr.

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: March 23, 2017
• Study Start: June 28, 2017
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: May 11, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)