To assess the safety and feasibility of a multimodal combination of FLOT CT with CROSS
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the feasibility of the combined regimens (defined as the
number of patients that complete the administration of four cycles of FLOT CT
and the full CROSS CRT regimen).
Secondary outcome
Secondary outcomes are the number of patients that have progressive disease
after four cycles of FLOT CT, disease control rate (DCR) and objective response
rate (ORR), both according to RECIST 1.1, serious adverse events and adverse
events according to Common Terminology Criteria for Adverse Events (CTCae)
v4.0, cumulative administered dose of FLOT and number of cycles of
carboplatin/paclitaxel administered as part of CROSS CRT, progression free
survival [PFS], overall survival [OS], number of patients with a clinically
complete response, QoL, the number of patients proceeding to local therapy of
distant metastases and/or oesophagectomy and tolerability of the combined
regimens of 4x FLOT CT followed by CROSS CRT followed by another 4x FLOT CT
(defined as the number of patients that complete the administration of four
cycles of FLOT, CROSS CRT and another four cycles of FLOT).
Background summary
Metastatic adenocarcinoma of the oesophagus or gastro-oesophageal junction
(GOJ) has a dismal prognosis and is associated with a poor quality of life
(QoL), mainly due to locoregional complaints such as dysphagia and odynophagia.
The recently published FLOT3- study showed that in selected patients with
limited metastatic disease, induction chemotherapy followed by surgery may
prolong survival. Furthermore, in the (potentially) curatively treated
patients, chemotherapy (CT), consisting of a combination of Fluorouracil,
Leucovorin, Oxaliplatin and doceTaxel (FLOT) is currently a standard of care as
peri-operative treatment for adenocarcinomas of the stomach and GOJ. On the
other hand, neoadjuvant chemoradiation (CRT) according to the CROSS regimen
improves locoregional control, QoL and survival in patients with resectable
oesophageal and GOJ tumours. After CRT, 23% of patients have a pathologically
complete response (pCR). The combination of systemic CT (FLOT) with mainly
locoregional acting CRT (CROSS) is an attractive treatment option for patients
with limited metastatic disease, aiming for better survival, but also better
locoregional control and thus improved QoL. It is currently unknown however
whether FLOT CT can be safely combined with CROSS CRT. This phase II study
investigates the safety and feasibility of the combined, sequenced regimen
Study objective
To assess the safety and feasibility of a multimodal combination of FLOT CT
with CROSS
Study design
Phase II, prospective single-centre intervention study
Intervention
In total 20 patients with limited distant metastatic disease will be included.
All patients will start with four courses of FLOT in 2-week cycles. A first
clinical response evaluation (CRE) will take place 4-6 weeks after the last CT
cycle using CT-neck/chest/abdomen. Patients with progressive disease will be
excluded from further study and treated according to the decision of the
multidisciplinary tumour board. Patients with stable or regressive disease will
continue with CROSS CRT (weekly administration of five cycles of carboplatin
and paclitaxel with concurrent radiotherapy). A second CRE (CRE2) will take
place 4-6 weeks after the last CRT session using a combination of
oesophago-gastro-duodenoscopy (OGD) with bite-on-bite biopsies, endosonography
(EUS) with fine needle aspiration (FNA) of suspicious nodes and CT
neck/chest/abdomen. QoL will be measured using questionnaires on three
time-points (pre-treatment and both CREs). After this time-point in the study,
further treatment, if any, is determined in our multidisciplinary tumour board
according to guidelines and institutional practice and not by the study
protocol. The options include best supportive care, continuation of
chemotherapy and treatment of the primary tumour and/or metastases (by local
ablative therapies and/or surgery).
Study burden and risks
The main burden for patients participating in this study is the possible
additional side effects due to the sequenced combination of two standard-used
regimens consisting of CT (FLOT) with CRT (CROSS) and additional diagnostic
tests (EUS and OGD with bite-on-bite biopsies). Furthermore, patients are asked
to fill out QoL questionnaires at three different time points. Stopping rules
have been incorporated to ensure patient safety.
dr. Molenwaterplein 40
Rotterdam 3015GD
NL
dr. Molenwaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- adenocarcinoma of the esophagus or gastro-esophageal junction with limited
but distant retroperitoneal and/or supraclavicular lymphatic dissemination
and/or maximum of 4 oligo metastases
- resectable primary esophageal tumor
- age 18-75
ECOG performance status 0-1
No prior radiotherapy or chemotherapy
Exclusion criteria
Polyneuropathy grade 1 or higher
Secondary primary cancer
Clinically significant cardiac disease (e.g. symptomatic coronary artery
disease or myocardial infarction within last 12 months)
Clinically significant pulmonary disease (Forced expiratory volume in 1 second
<1.5l)
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 | EUCTR2020-003605-55-NL |
| CCMO | NL74556.078.20 |