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A Phase I Study of High Dose Simvastatin in Patients With Gastrointestinal Tract Cancer Who Failed to Standard Chemotherapy

Primary Purpose

Stomach Cancer

Status

Unknown status

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Simvastatin

About this trial

This is an interventional treatment trial for Stomach Cancer

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Be willing and able to provide written informed consent/assent for the trial.
Be 20 years of age on day of signing informed consent
Have histologically or cytologically confirmed diagnosis of colorectal cancer or gastric cancer
For colorectal cancer, patients who progressed after 5FU or capecitabine, irinotecan,oxaliplatin, bevacizumab and cetuximab treatment (cetuximab is only for KRAS/NRAS wild type)
For gastric cancer, patients who progressed after second line chemotherapy.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Have evaluable disease based on RECIST v1.1 as determined by investigator.
Be willing to provide blood sample for PK analysis.
Ability to swallow and retain oral medication.
Demonstrate adequate organ function

Exclusion Criteria:

Prior history of statins within 12 months from the date of study entry
Patients with massive ascites or disseminated bone metastases
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Patients with CPK > ULN at baseline

Sites / Locations

Samsung Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

simvastatin

Arm Description

One arm Simvastatin 5-10mg/kg bid for 7 days and 14 days off treatment for 21 days Cohort 1: 7.5 mg/kg bid for 7 days 14 days off Cohort 2: 10 mg/kg bid for 7 days 14 days off Cohort 3: ( ) mg/kg bid for 7 days 14 days off (to be determined based on PK data of cohort 1 and 2) Q 3 weeks

Outcomes

Primary Outcome Measures

maximum tolerated dose

Secondary Outcome Measures

Full Information

NCT ID

NCT03086291

First Posted

March 16, 2017

Last Updated

December 26, 2019

Sponsor

Samsung Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03086291

Brief Title

A Phase I Study of High Dose Simvastatin in Patients With Gastrointestinal Tract Cancer Who Failed to Standard Chemotherapy

Official Title

A Phase I Study of High Dose Simvastatin in Patients With Gastrointestinal Tract Cancer Who Failed to Standard Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Unknown status

Study Start Date

January 4, 2018 (Actual)

Primary Completion Date

September 2020 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Samsung Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Simvastatin 5-10mg/kg bid for 7 days and 14 days off treatment for 21 days Cohort 1: 7.5 mg/kg bid for 7 days 14 days off Cohort 2: 10 mg/kg bid for 7 days 14 days off Cohort 3: ( ) mg/kg bid for 7 days 14 days off (to be determined based on PK data of cohort 1 and 2) Q 3 weeks

Detailed Description

This is a Phase 1, open-label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of high dose simvastatin in patients with GI cancers. Three dose levels will be evaluated. Simvastatin will be given at escalating dose of 7.5mg/kg bid, 10mg/kg bid and ( ) mg/kg bid for 7 days and off treatment for 14 days (Final dose will be determined based on PK data of cohort 1 and 2). The treatment will be repeated every 3 weeks. The cohort size of at least 3 and up to 6 patients ('rolling six design') will be employed to improve the rate of accrual of patients to cohorts close to the presumed therapeutic dose by reducing the need for late replacement of patients who become non-evaluable during the DLT assessment period, whilst not compromising collection of safety data. The total number of patients will depend upon the number of dose adjustments necessary. And intra-patient dose escalation is not allowed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stomach Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Simvastatin 5-10mg/kg bid for 7 days and 14 days off treatment for 21 days

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

simvastatin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Simvastatin

Intervention Description

Simvastatin 5-10mg/kg bid for 7 days and 14 days off treatment for 21 days

Primary Outcome Measure Information:

Title

maximum tolerated dose

Description

maximum tolerated dose

Time Frame

12months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Be willing and able to provide written informed consent/assent for the trial. Be 20 years of age on day of signing informed consent Have histologically or cytologically confirmed diagnosis of colorectal cancer or gastric cancer For colorectal cancer, patients who progressed after 5FU or capecitabine, irinotecan,oxaliplatin, bevacizumab and cetuximab treatment (cetuximab is only for KRAS/NRAS wild type) For gastric cancer, patients who progressed after second line chemotherapy. Have a performance status of 0 or 1 on the ECOG Performance Scale. Have evaluable disease based on RECIST v1.1 as determined by investigator. Be willing to provide blood sample for PK analysis. Ability to swallow and retain oral medication. Demonstrate adequate organ function Exclusion Criteria: Prior history of statins within 12 months from the date of study entry Patients with massive ascites or disseminated bone metastases Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Has an active infection requiring systemic therapy. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Patients with CPK > ULN at baseline

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

wonki kang, ph.D

Phone

82-2-3410-3459

wonki.kang@samsung.com

Facility Information:

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

135-720

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Won Ki Kang, MD

wonki.kang@samsung.com

First Name & Middle Initial & Last Name & Degree

Won Ki Kang, MD

12. IPD Sharing Statement

Learn more about this trial

A Phase I Study of High Dose Simvastatin in Patients With Gastrointestinal Tract Cancer Who Failed to Standard Chemotherapy

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