RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer - Full Text View

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:

MedlinePlus related topics: Cancer Stomach Cancer

Drug Information available for: Sirolimus Oxaliplatin Capecitabine Everolimus Temsirolimus

Genetic and Rare Diseases Information Center resources: Stomach Carcinoma

U.S. FDA Resources

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 ]


Enrollment:	40
Study Start Date:	February 2010
Study Completion Date:	September 2013
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

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:	January 11, 2015
Health Authority:	Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:


XELOX RAD001 phase 1

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on March 03, 2015