Phase I Study of Daily RAD001 in Combination With Mitomycin C in Patients With Advanced Gastric Cancer or Cancer of the Esophagogastric Junction (S387)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01042782
Recruitment Status : Completed
First Posted : January 6, 2010
Last Update Posted : August 3, 2012
Information provided by (Responsible Party):
Krankenhaus Nordwest

Brief Summary:
Patients with advanced gastric cancer are treated with a combination of RAD001 (everolimus) and Mitomycin C.

Condition or disease Intervention/treatment Phase
Advanced Gastric Cancer Advanced Cancer of the Esophagogastric Junction Drug: RAD001 and MitomycinC Phase 1

Detailed Description:
The purpose of this monocenter, single-arm, phase I trial is to determine the maximum-tolerated-dose, dose-limiting toxicity (DLT) and preliminary efficacy and safety of RAD001 in combination with Mitomycin C in patients with advanced gastric cancer.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Daily RAD001 Administered Orally in Combination With Mitomycin C, Administered Every Three Weeks to Patients With Advanced Gastric Cancer or Cancer of the Esophagogastric Junction
Study Start Date : January 2008
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: RAD-MitC
RAD001 orally daily 5mg or 7.5mg or 10mg Mitomycin C 5mg/m2 every 3 weeks
Drug: RAD001 and MitomycinC

RAD001 tablets daily, 5mg, 7.5 mg or 10 mg (3 cohorts)

Mitomycin C 5 mg/m2 i.v. every 3 weeks

Other Name: RAD001 (everolimus)

Primary Outcome Measures :
  1. maximum tolerated-dose (MTD) of RAD001 in combination with Mitomycin C [ Time Frame: every week ]

Secondary Outcome Measures :
  1. preliminary efficacy of RAD001 in refractory gastric cancer. Efficacy is defined as complete response or partial response at 12 weeks based on RECIST-criteria [ Time Frame: every 6 weeks ]
  2. progression-free survival (PFS) [ Time Frame: every 6 weeks ]
  3. overall survival (OS) [ Time Frame: every three months ]
  4. safety and tolerability of the combination of RAD001 and Mitomycin C as assessed by frequency, severity, and duration of treatment-related adverse effects [ Time Frame: every week ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 1 prior platin containing chemotherapy in the palliativ setting or progressive disease under adjuvant or neoadjuvant therapy within 6 months of treatment start date.
  • Histological evidence of advanced or metastatic gastric cancer or cancer of the esophageal junction.
  • At baseline CT or MRI scan must demonstrate measurable disease by RECIST criteria, i.e., the presence of at least one measurable lesion. Measurable disease lesions must be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques or > 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness).
  • At least one measurable lesion outside of the field of any prior radiation therapy (according to RECIST criteria). Prior radiotherapy to a single index lesion is not allowed.
  • Adult male or female patients (≥18 years of age).
  • Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent.
  • ECOG 0 or 1
  • Life expectance >4 months
  • Adequate bone marrow function, renal function, liver function
  • Women using an acceptable form of contraception prior to receiving RAD001 or women who meet the protocol definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy.
  • Fully recovered from any previous surgery, prior chemotherapy or radiation therapy (at least 4 weeks since major surgery or prior myelosuppressive chemotherapy). With the exception of alopecia, patients must have resolution of all acute toxic effects of any prior surgery, radiotherapy, or chemotherapy to NCI CTC (Version 2.0) grade <=1. Patients with rapidly progressive tumors (upon the decision of the investigator) can be treated <4 weeks since last chemotherapy, if they fully recovered from all side effects.
  • Signed informed consent

Exclusion Criteria:

  • Anticancer therapy within 3 weeks of enrollment including chemotherapy, hormonal therapy, immunotherapy, or radiotherapy. Patients with rapidly progressive tumors (upon the decision of the investigator) can be treated <4 weeks since last chemotherapy, if they fully recovered from all side effects.
  • Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).
  • Patients treated with Mitomycin C
  • No neurotoxicity >= grade 2 CTC
  • No gastric or intestinal obstruction
  • Patients taking drugs known to inhibit or induce isoenzyme CYP3A
  • Patients with any concurrent major medical condition liable to compromise the patient's participation in the study (e.g known HIV infection, uncontrolled diabetes, serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure, myocardial infarction within 6 months, unstable angina, chronic or acute renal or liver disease, uncontrolled serious infections including abscess or fistulae, etc.)
  • Patients with a history of another malignancy prior to study entry, except curatively treated non-melanotic skin cancer or carcinoma in-situ cervical cancer unless in complete remission or no evidence of disease and off all therapy for that disease for a minimum of 5 years
  • No symptomatic brain metastasis.
  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  • Female patients who are pregnant or breast feeding
  • History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures
  • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01042782

Krankenhaus Nordwest
Frankfurt, Germany, 60488
Sponsors and Collaborators
Krankenhaus Nordwest
Principal Investigator: Salah-Eddin Al-Batran, MD Krankenhaus Nordwest

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Krankenhaus Nordwest Identifier: NCT01042782     History of Changes
Other Study ID Numbers: CRAD001C24126
First Posted: January 6, 2010    Key Record Dates
Last Update Posted: August 3, 2012
Last Verified: August 2012

Keywords provided by Krankenhaus Nordwest:
gastric cancer
Mitomycin C

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors