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

NCT02383368 | Completed Phase 1

• 1 other identifier: 4132-CL-0001
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Lymphoma; Refractory Solid Tumors; Advanced Cancer

Keywords

Pharmacokinetics; ASP4132; Lymphoma; Refractory Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Safety as assessed by adverse events

  up to 39 months

• Safety as assessed by clinical laboratory tests

  up to 39 months

• Safety as assessed by vital signs

  up to 39 months

• Safety as assessed by electrocardiograms (ECG)

  up to 39 months

Secondary Outcomes (13)

• Objective response rate to ASP4132

  Week 16

• Duration of response to ASP4132

  Week 16

• Disease control rate to ASP4132

  Week 16

• Maximum concentration (Cmax) of ASP4132

  up to 43 days

• Time of the maximum concentration (Tmax) of ASP4132

  up to 43 days

Study Arms (2)

ASP4132 dose escalation

EXPERIMENTAL

Subjects will receive a single dose of the study drug on Day -4 (Single-Dose Period), followed by PK sampling prior to Multiple-Dose Period where they will receive the same dose as they received in the Single-Dose Period on one of four schedules: Continuous - daily dosing for 28 days, Intermittent: Schedule A: 3 days on / 4 days off; Schedule B: 1 days on / 6 days off; Schedule C: 3 days on / 11 days off.

Drug: ASP4132

ASP4132 dose expansion

EXPERIMENTAL

Subjects in Part 2 will be treated with ASP4132 at the MTD and dosing schedule identified from Part 1.

Drug: ASP4132

Interventions

ASP4132 DRUG

oral

ASP4132 dose escalation; ASP4132 dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (5)

Site US10001

New Haven, Connecticut, 06520, United States

Location

Site US10004

Chicago, Illinois, 60637, United States

Location

Site US10002

Rochester, Minnesota, 55905, United States

Location

Site US10003

Houston, Texas, 77030, United States

Location

Site US10005

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Janku F, LoRusso P, Mansfield AS, Nanda R, Spira A, Wang T, Melhem-Bertrandt A, Sugg J, Ball HA. First-in-human evaluation of the novel mitochondrial complex I inhibitor ASP4132 for treatment of cancer. Invest New Drugs. 2021 Oct;39(5):1348-1356. doi: 10.1007/s10637-021-01112-7. Epub 2021 Apr 8.

  PMID: 33830407 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Lymphoma

Interventions

ASP4132

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 9, 2015
• Study Start: March 23, 2015
• Primary Completion: April 27, 2018
• Study Completion: April 27, 2018
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)