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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01049620
First received: January 13, 2010
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Advanced Gastric Cancer
Drug: RAD001, Capecitabine, Oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Finding Study of RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • To assess the maximum tolerated dose (MTD) [ Time Frame: 1year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Biomarker study [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049620

Locations
Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Yoon-Koo Kang, MD, PhD Asan Medical Center
  More Information

No publications provided

Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01049620     History of Changes
Other Study ID Numbers: AMC-ONCGI-0905
Study First Received: January 13, 2010
Last Updated: March 27, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
XELOX
RAD001
phase 1

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Capecitabine
Sirolimus
Fluorouracil
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014