A Dose Escalation and Expansion Study of ASP4132 to Subjects With Advanced Refractory Tumors and Lymphoma

Lymphoma Clinical Trial

Official title:

An Open-Label, Dose-Escalation/Expansion Phase 1 Study of ASP4132 Given Orally to Patients With Advanced Refractory Solid Tumors and Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02383368
• Other study ID #: 4132-CL-0001
• Status: Completed
• Phase: Phase 1
• Start date: March 23, 2015
• Est. completion date: April 27, 2018

Study information

• Verified date: May 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability of ASP4132 and to determine the maximum tolerated dose and recommended phase 2 dose of ASP4132. The study will also determine the pharmacokinetics (PK) of ASP4132 and evaluate the preliminary antitumor activity.

Description:

The study consists of two parts and these will be conducted sequentially: Part 1 (dose escalation) and Part 2 (dose expansion). Subjects will participate in Part 1 or Part 2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: April 27, 2018
• Est. primary completion date: April 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject has a life expectancy of more than 3 months

• Subject agrees not to participate in another interventional study while on treatment.

• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status = 2.

• Female subject must be either:

1. Of non-child bearing potential:

• post-menopausal (defined as at least 1 year without any menses) prior to Screening,

• or, documented surgically sterile or status post hysterectomy

2. Or, if of childbearing potential,

• agree not to try to become pregnant during the study and for 90 days after the final study drug administration;

• if heterosexually active must use two forms of birth control

• Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.

• Subject must have advanced and/or metastatic, histologically or cytologically documented cancer or lymphomas, for whom there is no available standard therapy shown to provide clinical benefit.

Exclusion Criteria:

• Subject has absolute neutrophil count < 1000/µL, platelet count < 75,000/µL, and hemoglobin < 8 g/dL (< 5 mmol/L) at Screening

• Subject has total serum bilirubin =1.5 times the upper limit of normal (ULN),serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 times ULN, or albumin = 3.0 g/dL at Screening.

• Subject has any abnormalities in serum sodium, potassium, chloride, calcium and magnesium levels = Grade 2 at screening (CTCAE Version 4.03).

• Subject has a known elevation in serum lactate at screening ? 2x institutional ULN

• Subject has an estimated glomerular filtration rate (eGFr) of < 60ml/min as calculated by the modification of diet Renal disease (MDRD) Equation.

• Subject with a QTcF of > 450 msec in male subjects and > 470 msec in female subjects on the screening 12 lead ECG.

• Subject has Neuropathy = Grade 2 at Screening.

• Subject has Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus and currently being treated with insulin or sulfonylureas.

• Subject has concomitant active second malignancies unless remission was achieved at least 3 years prior to study entry and subject is no longer on therapy for the malignancy.

• Subject has a significant cardiovascular disease

• Subject has a known history of acute or chronic hepatitis B (HBV), HIV or hepatitis C (HCV) infection.

• Subject has serious/active bacterial, viral or fungal infection requiring systemic treatment.

• Subject has significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation.

• Subject has active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy (subjects must be off steroids). Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by brain MRI/CT.

• Subject has concurrent severe or uncontrolled medical disease or organ system dysfunction which, in the opinion of the Investigators, would limit life expectancy to < 3 months.

• Subject has psychiatric disorder or altered mental status that would preclude an understanding of the informed consent process and/or completion of the necessary study procedures.

• Subject has difficulty swallowing large pills.

• Subject currently being treated with biguanides or other agents known to increase risk of lactic acidosis.

• Subject has unavoidable concomitant treatment with any drug known for causing Torsades de Pointes.

• Subject has had radiotherapy or surgery within the 4 weeks prior to treatment with ASP4132.

• Subject has not discontinued all previous systemic therapies for cancer including chemotherapy, immunotherapy, or biological therapies for at least 14 days prior to the initiation of ASP4132.

• Subject has not fully recovered from the acute toxicities (except alopecia) of any prior anti-cancer therapy.

• Subject requiring concomitant use of strong CYP3A4 inhibitors or inducers.

Related Conditions & MeSH terms

• Advanced Cancer
• Lymphoma
• Refractory Solid Tumors

Intervention

Drug:
• ASP4132
oral

Locations

Country	Name	City	State
United States	Site US10004	Chicago	Illinois
United States	Site US10005	Fairfax	Virginia
United States	Site US10003	Houston	Texas
United States	Site US10001	New Haven	Connecticut
United States	Site US10002	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as assessed by adverse events		up to 39 months
Primary	Safety as assessed by clinical laboratory tests		up to 39 months
Primary	Safety as assessed by vital signs		up to 39 months
Primary	Safety as assessed by electrocardiograms (ECG)		up to 39 months
Secondary	Objective response rate to ASP4132		Week 16
Secondary	Duration of response to ASP4132		Week 16
Secondary	Disease control rate to ASP4132		Week 16
Secondary	Maximum concentration (Cmax) of ASP4132		up to 43 days
Secondary	Time of the maximum concentration (Tmax) of ASP4132		up to 43 days
Secondary	Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of ASP4132		up to 43 days
Secondary	AUC from the time of dosing to 24 hours (AUC24) of ASP4132		up to 43 days
Secondary	AUC from the time of dosing extrapolated to time infinity (AUCinf) of ASP4132		up to 43 days
Secondary	Apparent terminal elimination half-life (T1/2) of ASP4132		up to 43 days
Secondary	Accumulation ratio of ASP4132		up to 43 days
Secondary	Apparent total systemic clearance after single or multiple extravascular dosing (CL/F) of ASP4132		up to 43 days
Secondary	Apparent volume of distribution during the terminal elimination phase after single or multiple extravascular dosing (Vz/F) of ASP4132		up to 43 days
Secondary	Progression-free survival		up to 39 months

External Links

•   Link to results on the Astellas Clinical Study Results website