Clinical trial NCT01049620: RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer: RAD001+XELOX
Official title: A Phase I Dose Finding Study of RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Gastric Cancer
Keywords: XELOX
RAD001
phase 1
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2010-01-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: It is expected that RAD001 works in gastric cancer by inhibiting PI3K/AKT/mTOR pathway and Hif1A (hypoxia inducible factor 1, alpha subunit), a key player in angiogenesis and the growth of tumors like renal cell carcinoma.However, RAD001 alone looks not enough to control gastric cancer. By the mechanisms above, RAD001 can show additive or synergistic effect in combination with conventional chemotherapy. In this study, XELOX was selected as a conventional combination chemotherapy because it was proven very active and safe in gastric cancer. Combination of XELOX and RAD001 has been never tried for the treatment of cancer patients yet. So, the optimal dose will be first determined in this phase I study

Detailed description: For the first cohort of this phase I study, each drug of capecitabine, oxaliplatin, and RAD001 will be started at one or two dose below the ordinary full dose of each drug as a single agent.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically documented unresectable or metastatic adenocarcinoma of stomach or gastroesophageal junction
* No history of chemotherapy or radiation
* Age 18 to 70 years old
* Estimated life expectancy of at least 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Adequate bone marrow function (white blood cell counts \>3,000/uL, absolute neutrophil count\>1,500/uL, Platelets\>100,000/uL, Hgb\>8 g/dL)
* Adequate kidney function (creatinine\<1.5 mg/dL)
* Adequate liver function (bilirubin\<1.5 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level \<3 times the upper normal limit (5 times for patients with liver metastasis))
* Signed written informed consent

Exclusion Criteria:

* Past or concurrent history of neoplasm other than gastric adenocarcinoma except for curatively treated basal cell carcinoma of skin or in situ carcinoma of the cervix uteri
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start
* Presence of central nervous system metastasis
* Bowel obstruction
* Evidence of serious gastrointestinal bleeding
* Peripheral neuropathy (NCI CTC AE version 3.0 \> Grade I)
* History of significant neurologic or psychiatric disorders
* Pregnant or lactating women, women of childbearing potential not employing adequate contraception
* Other serious illness or medical conditions
* Patients with known history of ischemic heart disease and/or with myocardial infarction
* Known allergy to study drugs
* Administration of drugs showing interaction with RAD001

Primary outcomes:
measure: To assess the maximum tolerated dose (MTD)
timeFrame: 1year
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 1 year
measure: Biomarker study
timeFrame: 1 year
measure: Response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
Study officials:
affiliation: Asan Medical Center
name: Yoon-Koo Kang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: