Trial Title:
MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer
NCT ID:
NCT02007148
Condition:
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Docetaxel
Capecitabine
Conditions: Keywords:
gastric adenocarcinoma,
capecitabine,
second line treatment,
recurrent or metastatic disease,
overall survival,
tumor response,
quality of life
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
capecitabine
Description:
twice a day
Arm group label:
micado
Other name:
xeloda
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
cycles repeated every 3 weeks
Arm group label:
micado
Other name:
taxotere
Summary:
Second-line chemotherapy represents an option in gastric cancer, especially for patients with
adequate performance status. Two randomized phase III trials comparing 2nd-line docetaxel
with best-supportive care have reported a benefit in favor of chemotherapy. Capecitabine is a
fluoropyrimidine carbamate, which has a broader spectrum of antitumor activity than other
fluoropyrimidines. In gastric cancer xenografts. metronomic capecitabine inhibited
angiogenesis, growth of gastric cancer and improved survival with less toxicity. Given its
potential low toxicity, the combination of docetaxel and metronomic capecitabine needs to be
evaluated to assess efficacy and tolerability in patients with advanced gastric cancer
previously treated with a fluoropyrimidine-based and platinum-based chemotherapy.
Detailed description:
Despite a declining incidence in many developed countries, gastric cancer remains the second
most common cause of cancer deaths, and it is responsible for about 12% of all cancer-related
deaths worldwide. More than two-thirds of patients diagnosed with gastric cancer will have
unresectable disease and despite the fact that surgical pathological resection can be
curative for many patients, most of them develop recurrent disease. Evidence supports the use
of palliative chemotherapy with the aims of improving symptoms, quality of life, and possibly
prolonging survival. Combination chemotherapy regimens have been developed in the hopes of
improving response rate and overall survival (OS). Unfortunately, the benefits of combination
chemotherapy have been modest. In general, regimens containing fluoropyrimidine and platinum
agents are widely accepted as potential standard therapies. Although a large proportion of
patients with metastatic or recurrent gastric cancer may initially respond to chemotherapy,
they ultimately progress. In addition, many patients have primary refractory disease. The
median survival at progression after first-line chemotherapy for metastatic gastric cancer is
about 2.5 months.
Docetaxel is one of the most active single agents in the treatment of gastric cancer. In the
first line setting, at a dose of 60-100 mg/m2 repeated every 3 weeks, response rates ranged
from 17% to 20%. Docetaxel is the only taxane that has been evaluated in the context of a
phase III study.
Low-dose metronomic chemotherapy represents a new strategy to treat solid tumors by
exhibiting stronger anti-angiogenic activity and less side effects, especially in combination
with other anti-angiogenic agents. Capecitabine is a fluoropyrimidine carbamate, which has a
broader spectrum of antitumor activity than other fluoropyrimidines. In gastric cancer
xenografts. metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and
improved survival with less toxicity. In combination with other drugs, the treatment with
metronomic capecitabine has proven its efficacy with minimal toxicity in breast cancer, in
metastatic renal-cell carcinoma, in advanced adrenocortical carcinoma, in hepatocellular
carcinoma, in prostate cancer.
The "metronomic" strategy was also considered in pretreated elderly patients with advanced
gastric cancer. Eligible patients with advanced gastric cancer were treated with capecitabine
until disease progression or significant toxicity. Metronomic chemotherapy achieved a disease
control rate at 8 weeks of 51.1% , and the objective response rate was 20.9% . The median
time-to-progression and median overall survival were 3.6 months and 7.6 months, respectively.
Grade II neutropenia and thrombocytopenia were observed in 13.3 and 2.2% of patients,
respectively. Grade II/III nonhematological toxicities included diarrhea (4.4%), stomatitis
(13.4%), and hand-foot syndrome (15.5%). No grade 4 toxicity, neutropenic fever or
treatment-related deaths occurred.
Based on these premises and to the fact that the role of metronomic chemotherapy remains
controversial, its optimal therapeutic use has not yet been defined, we designed this phase
II study with tha aim to assess efficacy and tolerability of metronomic capecitabine in
combination with the conventional use of docetaxel in patients with advanced gastric cancer
previously treated with a fluoropyrimidine-based and platinum-based chemotherapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. At least 18 years of age
2. Histologically or cytologically confirmed gastric adenocarcinoma, including gastric or
gastroesophageal-junction adenocarcinoma (GEJ)
3. Measurable disease based on computed tomography
4. Eastern Cooperative Oncology Group performance status 0 or 1
5. Treatment with only 1 prior regimen (as first-line therapy) that must have included a
fluoropyrimidine and a platinum agent
6. Disease progression after the start of the prior regimen based on computed tomography
(or magnetic resonance imaging in the event of allergy to contrast medium)
7. Adequate bone marrow, hepatic, and renal function,
8. At least 4 weeks and recovery from effects of prior major surgery or radiation therapy
9. If previously administered as treatment for gastric cancer, prior to study entry a
washout period equivalent to at least 5 half-lives for antibodies and of at least 28
days for chemotherapy (Concurrent use of bisphosphonates is permitted.)
10. Ability to swallow an oral solid-dosage form of medication, including when a feeding
tube is present
11. A negative serum pregnancy test within 7 days prior to accrual in women of
childbearing potential
12. Agreement to use an effective form of contraception
13. Signed written informed consent.
14. Ability to comprehend and to comply with the requirements of the study.
Exclusion Criteria:
1. Squamous cell gastric carcinoma
2. Bone-only metastatic disease
3. History or presence of brain metastasis or leptomeningeal disease
4. Operable gastric or GEJ cancer
5. Herceptin 2 (HER2) -positive disease if the subject has not previously been treated
with an anti-HER2 agent
6. Uncontrolled diarrhea, defined as more than 3 loose bowel movements above the
subject's usual number of bowel movements on at least 3 days within the 14 days prior
to study entry
7. Nausea or vomiting for at least 3 consecutive days within the 14 days prior to study
entry despite the administration of standard antiemetic therapy
8. Known malabsorptive disorder
9. Second cancer (except for adequately treated basal cell or squamous cell skin cancer,
in situ cervical cancer, or other cancer for which the subject has been disease-free
for 5 or more years)
10. Human immunodeficiency virus infection based on history of positive serology
11. Significant medical disease other than gastric cancer, including but not limited to
uncontrolled diabetes mellitus, active angina or heart failure, uncontrolled
hypertension, or an active psychiatric condition that would prevent consistent and
compliant participation in the study
12. Presence of neuropathy > Grade 1
13. Prior treatment including docetaxel
14. Prior radiation therapy to more than 25% of the bone marrow
15. Need for other anticancer treatment (such as chemotherapy, radiation therapy, or
biologic therapy with an approved or investigational agent) while receiving protocol
therapy
16. History of severe or unexpected reaction to fluoropyrimidine therapy
17. History of hypersensitivity to fluoropyrimidine agents or any of their ingredients.
18. Known dihydropyrimidine dehydrogenase deficiency
19. Pregnancy or lactation
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
AORMN, Presidio Ospedaliero San Salvatore
Address:
City:
Pesaro
Zip:
61122
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Vincenzo Catalano, MD
Phone:
+39072136
Phone ext:
4001
Email:
catalano_v@yahoo.it
Investigator:
Last name:
Vincenzo Catalano, MD
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
Address:
City:
Pesaro
Zip:
61122
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Vincenzo Catalano, MD
Phone:
+39072136
Phone ext:
4001
Email:
catalano_v@yahoo.it
Investigator:
Last name:
Vincenzo Catalano, MD
Email:
Principal Investigator
Start date:
November 2013
Completion date:
May 2022
Lead sponsor:
Agency:
International Group of Endovascular Oncology
Agency class:
Other
Source:
International Group of Endovascular Oncology
Record processing date:
ClinicalTrials.gov processed this data on April 10, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02007148
http://igevo.jimdo.com/
