RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer: RAD001+XELOX

A Phase I Dose Finding Study of RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer

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

Study Overview

• Status: Completed
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Drug: RAD001, Capecitabine, Oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Xelox+RAD001

Drug: RAD001, Capecitabine, Oxaliplatin; Dose level -1 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 5mg po qd D1-21 Dose level 1 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 2 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 3 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 3A : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 10mg po qd D1-21 Dose level 3B : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 10mg po qd D1-21 Dose level 4 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 5 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 10mg po qd D1-21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the maximum tolerated dose (MTD)	1year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	1 year
Response rate	2 years
Progression-free survival	2 years
Biomarker study	1 year

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 13, 2010
• First Posted (Estimate): January 14, 2010

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: phase 1; RAD001; XELOX
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Capecitabine; Oxaliplatin; Everolimus
• Other Study ID Numbers: AMC0905