To estimate the treatment effect as measured by progression free survival(PFS) of subjects receiving AMG 386 (at 2 doses) in combination with cisplatin + capecitabinerelative to cisplatin + capecitabine + placebo
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Maag- en slokdarmkanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-free survival (PFS).
Secondary outcome
-Objective response Rate (ORR): the incidence of either a confirmed complete
response (CR) or partial response (PR) per modified RECIST criteria.
-Duration of response (DOR): (calculated only for those subjects with a
confirmed objective response) time from first confirmed objective response to
disease progression (per the modified RECIST criteria)
-Overall survival (OS): time from randomization date to date of death
-Incidence of AEs and significant laboratory changes from baseline
-Incidence of anti-AMG 386 antibody formation
-Time to progression (TTP): time from randomization to date of disease
progression per the modified RECIST criteria
-Time to response: time from randomization date to date of first objective
response for confirmed responders
-Change in tumor burden as measured by percentage change from baseline in the
sum of the longest diameters of target lesions
- Relative dose intensity of CX for the entire treatment period and over the
first 18 weeks of the treatment period.
- AMG 386 pharmacokinetic parameters when used in combination with capecitabine
and cisplatin
- Change in cancer-related symptoms as assessed with the QLQ-STO22
Exploratory:
-Baseline values and changes from baseline in pharmacodynamic markers as
assessed by blood levels of angiogenic cytokines (eg VEGF, bFGF, PIGF, Ang-1,
Ang-2)
-To evaluate the pharmacokinetics (PK) of capecitabine, its metabolite 5-FU and
cisplatin when used in combination with AMG386 in a sub-group of subjects at
selected sites
-Association of tumor apoptosis and other markers with response to treatment
-Baseline values and changes from baseline in immunologic, biochemical,
pharmacogenomic, and angiogenic markers in tumor biopsies or serum samples
-Change from baseline in cancer-related and treatment related symptoms and
health-related quality of life assessed with QLQ-STO22 and QLQ-C30
Change from baseline in the EuroQol EQ-5D summary score
Background summary
In this study, the study medication AMG 386 is evaluated for the treatment of
patients with metastatic gastric or esophageal cancer. AMG 386 is a man-made
medication that is designed to stop the development of blood vessels in cancer
tissues. Cancer tissues rely on the development of new blood vessels, a process
called angiogenesis, to obtain a supply of oxygen and nutrients to grow. AMG
386 is considered experimental (or investigational). AMG 386 is not approved by
any regulatory organization (such as the Food and Drug Administration, FDA) to
treat any type of cancer. AMG 386 will be evaluated in this study in
combination with cisplatin and capecitabine. Cisplatin in combination with
capecitabine is the standard treatment for patients with Metastatic Gastric,
Gastroesophageal Junction, and Distal Esophageal Adenocarcinoma. About 165
patients from 40 centers will participate in this study from regions including
the Unites States and Europe. Amgen Inc. a for-profit drug company, is funding
this clinical study.
Study objective
To estimate the treatment effect as measured by progression free survival
(PFS) of subjects receiving AMG 386 (at 2 doses) in combination with cisplatin
+ capecitabine
relative to cisplatin + capecitabine + placebo
Study design
This is a multicentre, randomized, phase 2 study. The study consists of 3 of
parts. The first part is the screening. If the patient is eligible for the
study, he/she will go into the treatment phase and this phase lasts until the
patients* cancer worsens, is unable to tolerate the investigational drug, or
decides to withdraw consent. After completion of the treatment, the patient
will be followed by the study staff by telephone or at routine clinic visits
approximately every 3 months for up to 4 years after the last subject starts
the study treatment (long term follow up). Each subject participating in this
clinical research study will receive 1 of the following treatments:
Arm A: - Cisplatin 80 mg/m² IV Q3W
- Capecitabine 1000 mg/m² PO BID x 14 days Q3W
- AMG 386 10 mg/kg IV QW.
Arm B: - Cisplatin 80 mg/m² IV Q3W
- Capecitabine 1000 mg/m² PO BID x 14 days Q3W
- AMG 386 3 mg/kg IV QW.
Arm C: - Cisplatin 80 mg/m² IV Q3W
- Capecitabine 1000 mg/m² PO BID x 14 days Q3W
- Placebo QW.
Intervention
Subjects will receive cisplatin/ capecitabine (Arms A, B, and C) in addition to
either blinded AMG 386 or placebo until they develop disease progression per
modified RECIST criteria, clinical progression, unacceptable toxicity, withdraw
consent, or death.
Study burden and risks
Estimated median length of subject treatment is 6 months for subjects on
cisplatin/ capecitabine plus placebo (Arm C), 8 months for subjects on
cisplatin/ capecitabine plus AMG 386 (Arms A and B). Safety follow up
assessments for each individual subject will be conducted 30 (+7) days after
discontinuation of all study drug (AMG 386 or placebo, cisplatin and
capecitabine). Subjects need to visit the clinic weekly during the treatment
phase, study visits with the subject receiving studymedication will last 4-6
hours.
Minervum 7061
4817 ZK Breda
NL
Minervum 7061
4817 ZK Breda
NL
Listed location countries
Age
Inclusion criteria
- Histologically or cytologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus with metastatic disease.
- 18 years of age or older at the time the written informed consent is obtained
- Subjects of child-bearing potential and sexually active must use an accepted and
effective non-hormonal method of contraception (ie, double barrier method [eg, condom plus diaphragm]) from signing the informed consent through 6 months following last administration of study drug
- Able to tolerate intravenous infusions
- Able to swallow oral medication
- ECOG of 0 or 1 (within 14 days prior to randomization)
- Adequate organ and hematological function as evidenced by laboratory studies
within 14 days prior to randomization.
For a complete list of all inclusion criteria please see protocol page 41 and 42.
Exclusion criteria
- Prior chemotherapy for metastatic disease (1st line)
- Less than 12 months have elapsed from completion of previous adjuvant or neoadjuvant chemotherapy or chemoradiotherapy
- Patients with persistant gastric outlet obstruction, complete dysphagia or feeding jejunostomy.
For a complete list of all exclusion criteria please see protocol page 42 and 43.
Design
Recruitment
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 | EUCTR2007-003573-50-NL |
| CCMO | NL20002.096.07 |
| Other | Nog niet bekend |