AzTrials
AzTrials

LymphomaPhase 1NCT02383368

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

A Phase 1 study testing ASP4132 in people with Lymphoma and Refractory Solid Tumors, run by Astellas Pharma Global Development, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Refractory Solid Tumors, Advanced Cancer
What is being tested?
ASP4132
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
5 sitesUnited States
Study dates
23 Mar 2015to 27 Apr 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Site US10004

    Chicago, Illinois, 60637

  • Site US10005

    Fairfax, Virginia, 22031

  • Site US10003

    Houston, Texas, 77030

  • Site US10001

    New Haven, Connecticut, 06520

  • Site US10002

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the detailed 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.

Being tested
ASP4132
Keywords
Pharmacokinetics, ASP4132, Lymphoma, Refractory Solid Tumors
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASP4132Drug

    oral

Study groups in NCT02383368
Study groupRoleWhat they receive
ASP4132 dose escalationExperimentalSubjects 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.
Receives: Drug: ASP4132
ASP4132 dose expansionExperimentalSubjects in Part 2 will be treated with ASP4132 at the MTD and dosing schedule identified from Part 1.
Receives: Drug: ASP4132

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety as assessed by adverse events

    Measured: up to 39 months

  2. Safety as assessed by clinical laboratory tests

    Measured: up to 39 months

  3. Safety as assessed by vital signs

    Measured: up to 39 months

  4. Safety as assessed by electrocardiograms (ECG)

    Measured: up to 39 months

Secondary outcomes (13)

  1. Objective response rate to ASP4132

    Measured: Week 16

  2. Duration of response to ASP4132

    Measured: Week 16

  3. Disease control rate to ASP4132

    Measured: Week 16

  4. Maximum concentration (Cmax) of ASP4132

    Measured: up to 43 days

  5. Time of the maximum concentration (Tmax) of ASP4132

    Measured: up to 43 days

  6. Area under the concentration-time curve from time of dosing to the last measurable concentration (AUClast) of ASP4132

    Measured: up to 43 days

  7. AUC from the time of dosing to 24 hours (AUC24) of ASP4132

    Measured: up to 43 days

  8. AUC from the time of dosing extrapolated to time infinity (AUCinf) of ASP4132

    Measured: up to 43 days

  9. Apparent terminal elimination half-life (T1/2) of ASP4132

    Measured: up to 43 days

  10. Accumulation ratio of ASP4132

    Measured: up to 43 days

  11. Apparent total systemic clearance after single or multiple extravascular dosing (CL/F) of ASP4132

    Measured: up to 43 days

  12. Apparent volume of distribution during the terminal elimination phase after single or multiple extravascular dosing (Vz/F) of ASP4132

    Measured: up to 43 days

  13. Progression-free survival

    Measured: up to 39 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2015 (estimated)
  2. Study start23 Mar 2015
  3. Primary completion27 Apr 2018
  4. Study completion27 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02383368
Sponsor's protocol ID
4132-CL-0001
Status last verified
Oct 2024
First submitted
4 Mar 2015
Last updated
31 Oct 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • 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.

    PubMed 33830407

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASP4132 in people with Lymphoma and Refractory Solid Tumors, run by Astellas Pharma Global Development, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as assessed by adverse events (time frame: up to 39 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02383368, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in