Assess the feasibility of preoperative treatment with pertuzumab and trastuzumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of withdrawal rate from surgery
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Feasibility of preoperative treatment with pertuzumab and trastuzumab combined
with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in
terms of withdrawal rate from surgery
Secondary outcome
• To assess toxicities of pertuzumab and trastuzumab alone and in combination
with chemoradiation.
• To assess post-operative complications.
• To assess pathological response.
• To assess R0 resection rate.
• To assess pharmacokinetics of pertuzumab and trastuzumab
Background summary
Despite neoadjuvant chemoradiation regimens, resectable 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 the
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 strategy. When the results of this study
show that this treatment strategy does not compromise the planned surgery, we
will subsequently design a prospective study with efficacy as primary
endpoint.
Study objective
Assess the feasibility of preoperative treatment with pertuzumab and
trastuzumab combined with preoperative chemoradiation (carboplatin, paclitaxel
and radiation) in terms of withdrawal rate from surgery
Study design
This is a non-randomized feasibility study a feasibility study with Paclitaxel
(T), Carboplatin (C), Pertuzumab (P), Trastuzumab (H), and radiation (RT)
followed by surgical resection of the oesophagus.
Intervention
Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous
infusion on days 1, 8, 15, 22 and 29. Trastuzumab will be administered at a
dose of 4 mg/kg on day 1, followed by 2 mg/kg at wk 2-6. From wk 7 onwards
trastuzumab is administered at a dose of 6 mg/kg every 3 weeks. Pertuzumab will
be given 840 mg intravenously at each administration.
Thus, trastuzumab and pertuzumab will be continued during eight weeks after the
end of chemoradiation. Surgery will be planned in or around week 14,
approximately eight weeks after the end of chemoradiation.
Study burden and risks
Trastuzumab and pertuzumab will be continued during eight weeks after the end
of chemoradiation.
Both the blood sample as the intravenous drip may be slightly painful and cause
a bruise at the puncture site . Furthermore, side effects occur, as a result of
pertuzumab and trastuzumab.
During an infusion of pertuzumab and trastuzumab chills, fever and other
flu-like symptoms may occur. The following symptoms are particularly with
pertuzumab very common : diarrhea , decrease in white blood cells , mucosal
inflammation, decreased appetite , vomiting , different taste perception,
anemia , diseases of the nails, physical weakness , rash , discomfort in the
fingers and feet , muscle pain , joint pain , colds or chest infections ,
dizziness and dry or itchy skin.
Heart problems can sometimes occur during treatment and sometimes after
treatment and can be severe. They include weakening of the heart muscle (which
can lead to heart failure ), inflammation of the pericardium , and cardiac
arrhythmias. This can lead to symptoms such as shortness of breath ( including
overnight ) cough , fluid retention ( swelling ) in the legs or arms . In rare
cases , patients treated with pertuzumab and trastuzumab had suffered from
heart failure .
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- 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, N0or 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 fulfilledT1N+ tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible.
- Tumor length longitudinal <= 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator .
- 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 years.
- ECOG performance status 0 or 1.
- Adequate hematological, renal and hepatic functions defined as:
o neutrophiles >= 1.5 x 109/L
o platelets >= 100 x 109/L
o hemoglobin >= 5.6 mmol
o total bilirubin <= 1.5 x upper normal limit
o creatinine clearance (Cockroft) > 60 ml/min
- Adequate left ventricular ejection fraction defined as an LVEF of >=55%.
- Written, voluntary informed consent.
Exclusion criteria
- 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 interfering with prognosis of esophageal cancer
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004111-42-NL |
| CCMO | NL46460.018.13 |