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

• Sponsor: Asan Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00729482
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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%.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasm	Drug: RAD001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of RAD001 (Everolimus) in Patients With Fluoropyrimidine and Platinum-refractory Advanced Gastric Cancer
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Rate at 4-month (16 Weeks) [4 months (16 weeks)]

   progression is definced as a more than 20% increase in one or more lesions or the appearance of any new lesion

Secondary Outcome Measures

1. Response Rate [2years]

   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.

2. Overall Survival [1 year]

3. Number of Participants With Adverse Events [up to 24 weeks]

   (according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center	Seoul	Songpa	Korea, Republic of	138-736

Sponsors and Collaborators

• Asan Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yoon-Koo Kang, Professor, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT00729482
• Other Study ID Numbers: AMC0801
• First Posted: Aug 7, 2008
• Last Update Posted: Jan 7, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Yoon-Koo Kang, Professor, Asan Medical Center: RAD001 (everolimus); second-line treatment; advanced gastric cancer
• Additional relevant MeSH terms: Stomach Neoplasms; Everolimus

Study Results

Participant Flow

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001) take RAD001 10mg/day dose (two 5mg tablets) orally evert day with a glass of water at the same time each day in a fasting state or with a light fat-free meal.
Period Title: Overall Study
STARTED	54
COMPLETED	54
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
Overall Participants	54
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	57.5
Sex: Female, Male (Count of Participants)
Female	9 16.7%
Male	45 83.3%
Region of Enrollment (participants) [Number]
Korea, Republic of	54 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
Measure Participants	54
Number [percentage of participants]	18.4 34.1%

2. Secondary Outcome

Title	Response Rate
Description	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.
Time Frame	2years

Outcome Measure Data

Analysis Population Description

51 patients were available for response assessments.

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
Measure Participants	51
Number [percentage of participants]	3.7 6.9%

3. Secondary Outcome

Title	Overall Survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
Measure Participants	54
Median (95% Confidence Interval) [Months]	8.3

4. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	(according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0)
Time Frame	up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
Measure Participants	54
Number [participants]	54 100%

Adverse Events

Time Frame	At least 6 months after last dose of chemotherapy.
Arm/Group Title	RAD001
Arm/Group Description	Treatment Arm (RAD001)
All Cause Mortality
	RAD001
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	RAD001
	Affected / at Risk (%)	# Events
Total	5/54 (9.3%)
Cardiac disorders
Sudden death	1/54 (1.9%)
Gastrointestinal disorders
Ileus	1/54 (1.9%)
Gastrointestinal bleeding	1/54 (1.9%)
Infections and infestations
Pneumonia	3/54 (5.6%)
Other (Not Including Serious) Adverse Events
	RAD001
	Affected / at Risk (%)	# Events
Total	54/54 (100%)
Blood and lymphatic system disorders
Neutropenia	23/54 (42.6%)
Anemia	51/54 (94.4%)
Thrombocytopenia	47/54 (87%)
Hemorrhage	18/54 (33.3%)
Gastrointestinal disorders
Diarrhea	19/54 (35.2%)
Constipation	15/54 (27.8%)
Anorexia	43/54 (79.6%)
Nausea	21/54 (38.9%)
Stomatitis	41/54 (75.9%)
General disorders
Asthenia	52/54 (96.3%)
Hepatobiliary disorders
Hyperbilirubinemia	14/54 (25.9%)
Elevated alkaline phosphatase	18/54 (33.3%)
Elevated aspartate aminotransferase	32/54 (59.3%)
Elevated alanine aminotransferase	20/54 (37%)
Elevated gamma glutamyl transpeptidase	17/54 (31.5%)
Metabolism and nutrition disorders
Hypercholesterolemia	24/54 (44.4%)
Triacylglyceridemia	13/54 (24.1%)
Hyperglycemia	47/54 (87%)
Hypophosphatemia	14/54 (25.9%)
Musculoskeletal and connective tissue disorders
Myalgia	20/54 (37%)
Renal and urinary disorders
Hyponatremia	24/54 (44.4%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	8/54 (14.8%)
Skin and subcutaneous tissue disorders
Skin rash	35/54 (64.8%)
Hand-foot syndrome	13/54 (24.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.