Phase II Trial of Vistusertib（AZD2014） Single Agent in TSC1or 2 Null or TSC 1/2 Mutation Solid Cancer Patients Refractory to Standard Chemotherapy (TSC1/2_SC)

SAMSUNG MEDICAL CENTER

Patients with TSC1/2 mutated refractory solid cancer will receive vistusertib(AZD2014) monotherapy. Study-arm is composed of 27 patients. Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle as a monotherapy

Study Overview

• Status: Withdrawn
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Vistusertib(AZD2014)

Detailed Description

Patients with TSC1/2 mutated refractory solid cancer will receive vistusertib(AZD2014) monotherapy. Study-arm is composed of 27 patients.

Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle as a monotherapy Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).

Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Patients may continue vistusertib(AZD2014) beyond progression (according to RECIST 1.1), at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.

If a patient discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Advanced solid cancers (including histologically or cytologically documented gastric cancer, colorectal cancer, hepatoma, biliary tract cancers, pancreatic cancer and rare cancers.) that has progressed after standard chemotherapy.
2. Provision of tumor sample (from either a resection or biopsy)
3. Patients with TSC1or 2 null or TSC 1/2 mutation through IHC.

4. Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:

   • Haemoglobin ≥9.0 g/dL (transfusion allowed)
   • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   • White blood cells (WBC) > 3 x 109/L
   • Platelet count ≥100 x 109/L (transfusion allowed)
   • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
   • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
   • Serum creatinine ≤1.5 x institutional ULN

Exclusion Criteria:

1. Any previous treatment with PIK3CA, AKT or mTOR inhibitor or agents with mixed PI3K / mTOR activity.

2. For vistusertib(AZD2014):

   Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if taken within the stated washout periods before the first dose of study treatment With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.

3. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective reponse rate (ORR) by RECIST 1.1	To investigate the efficacy and safety of vistusertib(AZD2014) single agent as salvage therapy in patients with TSC1or 2 null or TSC 1/2	12months

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2018
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (Actual): May 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 20, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2017-05-096

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No