Randomized, Double-Blind, Placebo Controlled Phase II Study of FOLFOX +/- Ziv-Aflibercept in Patients With Advanced Esophageal and Gastric Cancer
18 Years
N/A
Both
Esophageal Cancer, Gastric Cancer
Trial Information
Randomized, Double-Blind, Placebo Controlled Phase II Study of FOLFOX +/- Ziv-Aflibercept in Patients With Advanced Esophageal and Gastric Cancer
If patients agree to participate in this research study, they will be asked to undergo some
screening tests or procedures to find out if they are eligible. Many of these tests and
procedures are likely to be part of regular cancer care and may be done even if it turns out
that patients do not take part in this research study. If patients have had some of these
tests or procedures recently, they may or may not have to be repeated. These tests and
procedures include: a medical history, physical examination, EKG, CT, Blood tests, pregnancy
test, urine test, additional blood tests for research and a collection of archival tumor
tissue. The screening tests will be reviewed by the doctor and the study team and if the
patient meets the eligibility criteria for this study, they will begin treatment. If the
patient does not meet the eligibility criteria, they will not be able to participate in this
research study.
After the screening procedures confirm that a participant is eligible to participate in the
research study, they will be "randomized" into one of two groups. A participant will receive
either:
mFOLFOX6 with Ziv-aflibercept -or- mFOLFOX6 with Placebo (A Placebo contains no medicine)
Randomization means that a participant is put into a group by chance (like flipping a coin).
Neither the participant nor the research doctor will choose what group the participant will
be in. Randomization will be 2:1 (twice as many of the participants in this study will
receive mFOLFOX6+Ziv-aflibercept). This study is "blinded", which means neither the patient
nor the doctor will know if the patient is getting the investigational drug or the placebo
with the mFOLFOX6.
Before a participant begins mFOLFOX6 chemotherapy, they will have a central venous line
inserted for the intravenous (in a vein) chemotherapy administration. This is called a
"port" or vascular access device. Insertion of the port is a minor outpatient surgical
procedure that is performed by a surgeon or interventional radiologist depending on where it
is done. The doctor will arrange for the participant to have this procedure done before the
participant begins.
mFOLFOX6 is a combination of chemotherapy including oxaliplatin, leucovorin, and 5-FU. The
oxaliplatin and leucovorin are given intravenously over 2 hours. The 5-FU is also given
intravenously. The participant will get a shot of 5-FU by the infusion nurse and then will
be hooked up to a portable pump which will infuse the rest of the 5-FU slowly over the next
46-48 hours. The participant can either disconnect the pump at home, or return to the
infusion unit to have it disconnected. The participant, the caregivers and the nurse will
discuss the best option for disconnecting the pump and the patient will receive instructions
on how to do this at home, if applicable.
Ziv-aflibercept/Placebo will be given over 1 hour intravenously.
Inclusion Criteria:
- Confirmed adenocarcinoma of esophagus, GE junction or gastric origin
- Disease is not amenable to curative resection and is unresectable, locally advanced
or metastatic
- Have not received any prior chemotherapy, investigative or biologic agents for
esophagogastric cancer except in the neoadjuvant or adjuvant setting
- Any major surgery must be completed at least 4 weeks prior to study entry, minor
procedures must be completed at least 2 weeks prior to study entry
- Vascular access device insertion should be performed at least 1 week prior to study
entry. A central line is recommended for all participants
- Willing to use adequate contraception prior to study entry, for the duration of study
participation and for 3 months after the last dose of Ziv-aflibercept/placebo
Exclusion Criteria:
- History of hypertension unless adequately controlled
- Evidence of active bleeding from primary tumor at time of study entry
- Pregnant or breastfeeding
- Squamous cell carcinoma histology
- Prior treatment for advanced or metastatic disease
- Palliative radiation to < 25% of bone marrow must have been completed 2 weeks prior
to study entry, palliative RT to > 25% must have been completed 4 weeks prior to
study entry
- Known allergy to study agents
- Known dihydropyrimidine dehydrogenase deficiency or thymidylate kinase gene
polymorphism predisposing participant to 5-FU toxicity
- History of symptomatic congestive heart failure
- Clinically significant peripheral arterial disease
- Grade 2 or higher sensory or motor neuropathy
- Serious unhealed wound, ulcers or bone fractures
- History of HIV positivity or hepatitis B or C
- History of abdominal fistula, wound dehiscence, GI perforation, intra abdominal
abscess, uncontrolled GI bleeding or diverticulitis that required hospitalization
within 6 months of study entry
- History of arterial thrombotic events
- History of CNS hemorrhage in past 6 months
- Use of warfarin
- History of prior or synchronous malignancy except if treated with curative intent
more than 3 years prior to enrollment, or adequately treated non-melanoma skin
cancers, cervical carcinoma in situ or prostatic intraepithelial neoplasia without
evidence of prostate cancer
- Uncontrolled non-malignant illness
- Uncontrolled psychiatric illness
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Outcome Measure:
Estimate efficacy of Ziv-aflibercept+mFOLFOX6 in esophagogastric adenocarcinomas, as measured by progression-free survival (PFS).
Outcome Description:
To estimate the efficacy of Ziv-aflibercept used in combination with mFOLFOX6 in patients with previously untreated advanced esophagogastric adenocarcinoma, as measured by progression-free survival (PFS), measured from the date of initial treatment to first objective documentation of progressive disease or date of death, whichever occurs first.
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Peter Enzinger, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
12-401
NCT ID:
NCT01747551
Start Date:
January 2013
Completion Date:
Related Keywords:
- Esophageal Cancer
- Gastric Cancer
- Advanced
- Esophageal Diseases
- Esophageal Neoplasms
- Stomach Neoplasms
Name | Location |
|---|---|
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
