RAD001 (Everolimus) Salvage Monotherapy in Advanced Gastric Cancer (AGC) Who Failed Standard First-line Treatment

A Phase II Study of RAD001 (Everolimus) in Patients With Fluoropyrimidine and Platinum-refractory Advanced Gastric Cancer

This is a phase II study to evaluate RAD001 (Everolimus) in terms of 4-month progression-free survival rate (primary end-point) and response rate, toxicity, and overall survival (secondary end-points) in patients with metastatic and/or advanced inoperable gastric cancer.

Eligibility criteria include histologically proven gastric/gastroesophageal junction cancer who failed previous first-line standard treatment with fluoropyrimidine and platinum-based chemotherapy.

Oral RAD001 (everolimus) 10mg daily will be administered and the dose will be adjusted according to the observed clinical toxicities. Treatment will be continued until disease progression or patient's intolerability to the study drug.

Total of 54 patients will be enrolled to decide whether the proportion of patients who are free from progression at 4 months (16 weeks), P, is less that or equal to 0.15 or greater than or equal to 0.30 to assess the treatment outcome in 48 patients assuming drop-out rate, 10%.

Study Overview

• Status: Completed
• Conditions: Stomach Neoplasm
• Intervention / Treatment: Drug: RAD001

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Songpa
    • Seoul, Songpa, Korea, Republic of, 138-736
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction
• Patients must have non-resectable disease by metastasis or recurrent disease after curative surgical resection with uni-dimensionally measurable disease (at least longest diameter 1 cm on computed tomography scan, or at least 2 cm on chest x-ray or physical examination)
• Patients tumor should have failure of 1st line chemotherapy including fluoropyrimidine (5-FU, capecitabine, doxifluridine, S1, or UFT) and platinum (cisplatin, carboplatin, or oxaliplatin) in palliative setting; progression during or within 6 months after chemotherapy
• Age 18 to 75 years old
• Estimated life expectancy of more than 3 months
• ECOG performance status of 2 or lower
• Adequate bone marrow function
• Adequate kidney function
• Adequate liver function
• No prior radiation therapy to more than 25 percent of BM
• Patients must not have psychological, familial, sociological or geographical conditions which do not permit medical follow-up and compliance with this study
• Women of childbearing potential must have a negative pregnancy test on admission
• The patient must be able to understand the study and has given written informed consent to participate in the study

Exclusion Criteria:

• Other tumor types than adenocarcinoma
• Central nervous system metastases or prior radiation for CNS metastasis
• Gastric outlet obstruction or intestinal obstruction
• Evidence of active gastrointestinal bleeding
• Bony metastasis as the sole evaluable disease
• Past or concurrent history of neoplasm other than stomach cancer
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Thyroid disease

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: 1; Treatment Arm (RAD001)	Drug: RAD001; RAD001 (everolimus) 10mg daily administration orally until disease progression and/or intolerability; Other Names: everolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Rate at 4-month (16 Weeks)	progression is definced as a more than 20% increase in one or more lesions or the appearance of any new lesion	4 months (16 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		1 year
Response Rate	Tumor response is evaluated according to the new guidelines by RECIST criteria (See Appendix D). A complete response (CR) is defined as the disappearance of all evidence of cancer for 4 weeks or longer. A partial response (PR) is defined as a 30% or more reduction in the sum of the longest diameters of target lesions for 4 weeks or longer without any evidence of new lesions or progression of any lesions. Stable disease is defined as less than a 30% reduction or less than a 20% increase in the longest diameters of target lesions without any evidence of new lesions. Progressive disease is defined as a more than 20% increase in one or more lesions or the appearance of any new lesion.	2years
Number of Participants With Adverse Events	(according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0)	up to 24 weeks

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: August 4, 2008
• First Submitted That Met QC Criteria: August 4, 2008
• First Posted (Estimate): August 7, 2008

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: advanced gastric cancer; second-line treatment; RAD001 (everolimus)
• 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; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: AMC0801