RAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Yoon-Koo Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01482299
First received: November 3, 2011
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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, overall survival and biomarker assessment (secondary end-points) in patients with metastatic or recurrent gastric cancer with pS6 Ser 240/4 expression.

Eligibility criteria include pathologically proven non-resectable adenocarcinoma of stomach with measurable disease who failed previous first-line palliative chemotherapy including fluoropyrimidine and platinum with high expression of pS6 Ser 240/4.

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.

A study requires 40 assessable subjects to decide whether the proportion of patients who are free from progression at 4 months (16 weeks), P, is less than or equal to 0.1 or greater than or equal to 0.25 with a target error rate of 0.05 and β of 0.2. If the number of responses is 7 or less, the hypothesis that P >= 0.250 is rejected with a target error rate of 0.200 and an actual error rate of 0.182. If the investigators assume that drop-out rate is 10%, total accrual patient will be 45.


Condition Intervention Phase
Stomach Neoplasm
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of RAD001 (Everolimus) for 2nd Line Treatment After Failure of Fluoropyrimidine Plus Platinum Chemotherapy in Patients With Metastatic or Recurrent Gastric Cancer With pS6 Ser 240/4 Expression

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • 4-month progression-free survival [ Time Frame: up to 3years ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from the first treatment to the onset of progressive disease per RECIST criteria or to the date of death whichever comes first. For patients who do not experience progressive disease or death, the progression-free survival duration will be right censored on the last disease assessment date.


Secondary Outcome Measures:
  • Response rate [ Time Frame: Up to 1year ] [ Designated as safety issue: No ]
    evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0

  • Number of participants with adverse events [ Time Frame: Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment ] [ Designated as safety issue: Yes ]
    Adverse events will be graded according to Common Terminology Criteria for Adverse events version 4.0

  • Overall survival [ Time Frame: Up to 3years ] [ Designated as safety issue: No ]
    Overall survival duration is calculated as time from the first treatment to the date of death. For patients who are still alive at the cut‐off date for statistical reporting, the overall survival duration will be right censored on the last known alive date.

  • Biomarker assessment [ Time Frame: 24months ] [ Designated as safety issue: No ]
    Tumor tissues obtained by tumor tissues can be used for immunohistochemistry(IHC) of pS6 Ser 240/4. In patients who did not receive gastrectomy tumor biopsies will be obtained at screening(before everolimus treatment) and after two cycles of treatment. Scoring of all IHC results is based on the percentage of positive cells. The percentage of positive cells is scored as: 0 (0%); 1 (≤10%); 2 (11-33%); 3 (34-66%); 4 (≥67%).


Estimated Enrollment: 45
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 (everolimus) Drug: RAD001

RAD001 (everolimus) 10 mg daily, orally without interruption.

1 cycle is equal to 4-week treatment. Treatment will be continued unless disease progression or intolerability.

Other Name: everolimus

Detailed Description:

Methodology: Prospective, non blinded, open label, single center phase II study

Criteria for evaluation: Assessment of response will be assessed radiologically according to RECIST criteria after completion of the two cycles. Evaluation will be by physical examination, chest X-ray, abdomen-pelvis CT scan Safety criteria: Physical examination, vital signs, performance status, CBC, serum chemistry, NCI CTC V.3.0

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction
  • non-resectable disease by metastasis or recurrent disease after curative surgical resection (See Appendix A) with uni-dimensionally measurable disease
  • failure of 1st line chemotherapy including fluoropyrimidine (capecitabine, S1, or 5-FU,) and platinum (cisplatin or oxaliplatin) in palliative setting; progression during or within 6 months after chemotherapy
  • High expression of pS6 Ser 240/4 (proportion of pS6 Ser 240/4 positive cancer cells by immunohistochemistry > 10%)
  • Age 20 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
  • Fasting serum cholesterol ≤ 300 mg/dL AND fasting triglyceride ≤ 2.5 X ULN
  • No prior radiation therapy to more than 25% of BM
  • 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
  • Written informed consent

Exclusion Criteria:

  • Other tumor type than adenocarcinoma
  • CNS metastases or prior radiation for CNS metastases
  • Gastric outlet obstruction or intestinal obstruction
  • Evidence of active gastrointestinal bleeding
  • Bone lesions 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
  • Other serious illness or medical conditions
  • Concomitant or with a 4-week period administration of any other experimental drug under investigation
  • Concomitant chemotherapy, hormonal therapy, or immunotherapy
  • Any preexisting medical condition of sufficient severity to prevent full compliance with the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01482299

Locations
Korea, Republic of
Asan Medical Center
Songpa-gu, Seoul, Korea, Republic of
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: NCT01482299     History of Changes
Other Study ID Numbers: AMC-ONCGI-1104
Study First Received: November 3, 2011
Last Updated: March 27, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
pS6 Ser 240/4
RAD001 (everolimus)
second-line treatment
advanced gastric cancer

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

ClinicalTrials.gov processed this record on April 16, 2014