Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma

NCT02120911 | Completed Phase 1 DMC

• 2 other identifiers: AMCMEDONC 2013-3772013-004111-42
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Despite neoadjuvant chemoradiation regimens esophageal cancer remains a disease with poor outcome. The clinical benefit of HER2 targeting with trastuzumab has been shown in the setting of advanced disease and disease and safety of combining trastuzumab with chemoradiation in the curative setting has been established. In breast cancer, the added value of pertuzumab to standard treatment with trastuzumab has been shown both in the neoadjuvant and the metastastic setting. Taken together, there is a sound rationale to explore the combination of radiotherapy plus chemotherapy with trastuzumab and pertuzumab in HER2+resectable esophageal cancer. However, since the number of HER2+ patients in this setting is limited, and no data are available on the safety of this combination prior to major surgery, we propose to first conduct a feasibility study with this treatment stratgy. When the results of this study show that this treatment strategy is feasible, we will subsequently design a prospective study with efficacy as primary endpoint.

Conditions

Esophageal Carcinoma

Keywords

Her2+; Resectable esophageal carcinoma; Pertuzumab; Trastuzumab

Outcome Measures

Primary Outcomes (1)

• % of patients completing trastuzumab and pertuzumab treatment.

  See title

  up to 14 weeks after start of treatment

Secondary Outcomes (5)

• Toxicity of pertuzumab and trastuzumab alone and in combination with chemoradiation

  up to 14 weeks after start of treatment

• Number of post-operative complications

  up to 3 months after surgery

• Pathological response

  up to 2 weeks after surgery

• R0 resection rate

  up to 2 weeks after surgery

• Pharmacokinetics of pertuzumab and trastuzumab

  up to 14 weeks after start of treatment

Other Outcomes (3)

• Relation between exposure and effect (safety and efficacy).

  up to 3 months after surgery

• Biomarker analyses

  up to 3 months after surgery

• SUV of pre-treatment trastuzumab-PET

  up to two weeks after surgery

Study Arms (1)

Pertuzumab, trastuzumab

EXPERIMENTAL

Pertuzumab, trastuzumab

Drug: Pertuzumab, trastuzumab

Interventions

Pertuzumab, trastuzumab DRUG

Pertuzumab and trastuzumab will be combined with standard chemoradiation with carboplatin and paclitaxel.

Also known as: Perjeta, Herceptin

Pertuzumab, trastuzumab

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 intrathoracic esophagus or gastro esophageal junction.
• HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy.
• Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen.
• T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible.
• Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm.
• If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach.
• No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
• Age ≥ 18 and ≤ 75 years.
• ECOG performance status 0 or 1.
• 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

You may not qualify if:

• A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer.
• Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment.
• 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, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors.
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization.
• Pulmonary fibrosis and/or severely impaired lung function.
• Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.
• Active infection or other 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Roche Pharma AG: collaborator

Study Sites (1)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

Location

Related Publications (1)

• Stroes CI, Schokker S, Creemers A, Molenaar RJ, Hulshof MCCM, van der Woude SO, Bennink RJ, Mathot RAA, Krishnadath KK, Punt CJA, Verhoeven RHA, van Oijen MGH, Creemers GJ, Nieuwenhuijzen GAP, van der Sangen MJC, Beerepoot LV, Heisterkamp J, Los M, Slingerland M, Cats A, Hospers GAP, Bijlsma MF, van Berge Henegouwen MI, Meijer SL, van Laarhoven HWM. Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma: TRAP Study. J Clin Oncol. 2020 Feb 10;38(5):462-471. doi: 10.1200/JCO.19.01814. Epub 2019 Dec 6.

  PMID: 31809243 RESULT

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

pertuzumab; Trastuzumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• H. WM van Laarhoven, MD, PhD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, PhD

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 23, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: July 1, 2020

Record last verified: 2020-06

Locations

NL (1)