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Advanced Malignant Solid NeoplasmPhase 1NCT03291938

IACS-010759 in Advanced Cancers

A Phase 1 study testing Oxidative Phosphorylation Inhibitor IACS-010759, Pharmacodynamic Study and Pharmacokinetic Study in people with Advanced Malignant Solid Neoplasm and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

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

Official record
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Trial summary

This phase I trial studies the side effects and best dose of oxidative phosphorylation inhibitor IACS-010759 (IACS-010759) in treating patients with lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or solid tumors that have spread to other places in the body (advanced/metastatic) or… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oxidative Phosphorylation Inhibitor IACS-010759, Pharmacodynamic Study and Pharmacokinetic Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
13 Nov 2017to 23 Nov 2020
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

  • Non-pregnant.
  • Subjects must have histologically confirmed malignancy that is metastatic or unresectable and for which there is no available therapy likely to convey clinical benefit.
  • Subjects must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options are also eligible. a) Subjects with relapsed and/or refractory lymphoma must have had at least 2 prior lines of systemic therapy and are not candidates for high dose therapy/autologous stem cell transplant.
  • Subjects must have evaluable disease for the dose escalation, and measurable disease for the dose expansion.
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Subjects must have a life expectancy >= 12 weeks.
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  • Absolute neutrophil count >= 1,500/mcL.
  • Hemoglobin >= 9 g/dL.
  • Platelets >= 100,000/mcL.
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN).
  • Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 2.5 x institutional ULN or =< 5 x institutional ULN in the presence of liver metastases.
  • Creatinine clearance >= 45 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal.
  • Women of childbearing potential (WOCBP) must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: total abstinence when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
  • Combination of any of the two following (a+b or a+c or b+c): a) use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception; b) placement of an intrauterine device (IUD) or intrauterine system (IUS); c) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository. In case of use of oral contraception, women should have been stable on the same pill before taking study treatment.
  • Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Subjects must have disease that can be safely biopsied (for RP2D biopsy expansion cohort only), and agree to undergo a pretreatment and on-treatment biopsy.
  • Subjects with brain metastases must have completed treatment, either surgery or radiation, 4 weeks or longer prior to screening. A brain magnetic resonance imaging (MRI) demonstrating there is no current evidence of progressive brain metastases is required in subjects with previous brain metastasis. Patients with breast tissue expanders may have brain computerized tomography (CT) for assessment.
  • Subjects must not be on full dose oral anticoagulation such as warfarin. Low dose warfarin and prophylactic as well as therapeutic low molecular weight heparin are allowable.
  • Subjects who enroll in the triple-negative breast cancer (TNBC) dose expansion cohort should adhere to the American Society for Clinical Pathology (ASCP)/College of American Pathologists (CAP) guidelines for the definition of TNBC.
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Subjects who have had chemotherapy or radiotherapy within 3 weeks (4 weeks for immunotherapy; 6 weeks for nitrosoureas or mitomycin C) prior to starting the study agent.
  • Subjects with active brain metastases.
  • Subjects may not be receiving any other investigational agents or have participated in any other clinical trial involving another investigational agent for treatment of advanced solid tumors or lymphoma within 3 weeks prior to cycle 1, day 1 of the study.
  • Subjects who had major surgery or radiation therapy within 4 weeks of the first dose of study drug, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass.
  • Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to IACS-010759.
  • Subjects receiving metformin or other agents known to increase risk of lactic acidosis.
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  • Subjects who previously received IACS-010759 or oxidative phosphorylation (OXPHOS) inhibitors.
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active serious bacterial, fungal or viral infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subjects with a history of significant cardiac disease including: congestive heart failure requiring therapy; history of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment; clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block); left ventricular ejection fraction (LVEF) < 50% evaluated by echocardiogram (ECHO) or multigated acquisition scan (MUGA); increased Fridericia's correction formula (QTcF) (> 450 for men and > 470 for women).
  • Women who are breast-feeding or pregnant as evidenced by positive serum or urine pregnancy test performed within 72 hours of first dosing. (Pregnant women are excluded from this study because it is not known whether IACS-010759 has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IACS-010759 breastfeeding should be discontinued if the mother is treated with IACS-010759.)
  • Subjects with significant gastrointestinal abnormalities that may affect absorption (e.g., gastric bypass, short gut syndrome).
  • Subjects with known human immunodeficiency virus (HIV), acute chronic hepatitis B virus surface antigen (HBsAg) or hepatitis C virus. (HIV-positive subjects are ineligible because of the potential for pharmacokinetic interactions of antiviral therapy with IACS-010759.)
  • Lactic acid levels > 2 mmol/L and/or serum pH < 7.35 at baseline.
  • Subjects with other active malignancy in the past 3 years with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, in situ cervical cancer, or another early stage cancer that in the discretion of the investigator(s) is currently in complete remission.
  • Subjects with >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicity (except alopecia) due to prior cancer therapy.
  • Subjects with any concomitant disease or condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
  • Subjects with >= grade 1 peripheral neuropathy at screening.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of IACS-010759 in Subjects With Advanced Solid Tumors and Lymphoma

This phase I trial studies the side effects and best dose of oxidative phosphorylation inhibitor IACS-010759 (IACS-010759) in treating patients with lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or solid tumors that have spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). IACS-010759 may stop the growth of cancer or tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of IACS-010759, the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in subjects with any advanced solid tumor and lymphoma.

SECONDARY OBJECTIVES:

  1. To evaluate IACS-010759 pharmacokinetics and preliminary antitumor activity (including overall response rate and duration of response).

EXPLORATORY OBJECTIVES:

  1. To evaluate pharmacodynamic and exploratory predictive biomarkers of activity of IACS-010759.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 orally (PO) once daily (QD) on days 1-7 of cycle 1 in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 8 and 15 of cycle 1 and then on days 1, 8, and 15 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.

Being tested
Oxidative Phosphorylation Inhibitor IACS-010759, Pharmacodynamic Study, Pharmacokinetic Study
Medical subject headings
Neoplasm Metastasis, Lymphoma, Pancreatic Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • Oxidative Phosphorylation Inhibitor IACS-010759Drug

    Also called IACS-010759, OXPHOS Inhibitor IACS-010759

    Given PO

  • Pharmacodynamic StudyOther

    Also called PHARMACODYNAMIC

    Correlative studies

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

Study groups in NCT03291938
Study groupRoleWhat they receive
Treatment (oxidative phosphorylation inhibitor IACS-010759)ExperimentalINDUCTION PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 1-7 of cycle 1 in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive oxidative phosphorylation inhibitor IACS-010759 PO QD on days 8 and 15 of cycle 1 and then on days 1, 8, and 15 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Oxidative Phosphorylation Inhibitor IACS-010759; Other: Pharmacodynamic Study; Other: Pharmacokinetic Study

What is being measured

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

  1. Incidence of adverse events

    Measured: Up to 2 years

  2. Maximum tolerated dose

    Measured: Up to day 21

Secondary outcomes (3)

  1. Maximum Plasma concentration of IACS-010759 [Cmax]

    Measured: Up to 2 years

  2. Overall response rate

    Measured: Up to 2 years

  3. Duration of response

    Measured: Up to 2 years

Timeline

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

  1. First posted25 Sep 2017
  2. Study start13 Nov 2017
  3. Primary completion23 Nov 2020
  4. Study completion23 Nov 2020

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03291938
Sponsor's protocol ID
2017-0023
Other IDs
NCI-2018-01042, 2017-0023, P30CA016672
Status last verified
Nov 2020
First submitted
20 Sep 2017
Last updated
24 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Yap TA, Daver N, Mahendra M, Zhang J, Kamiya-Matsuoka C, Meric-Bernstam F, Kantarjian HM, Ravandi F, Collins ME, Francesco MED, Dumbrava EE, Fu S, Gao S, Gay JP, Gera S, Han J, Hong DS, Jabbour EJ, Ju Z, Karp DD, Lodi A, Molina JR, Baran N, Naing A, Ohanian M, Pant S, Pemmaraju N, Bose P, Piha-Paul SA, Rodon J, Salguero C, Sasaki K, Singh AK, Subbiah V, Tsimberidou AM, Xu QA, Yilmaz M, Zhang Q, Li Y, Bristow CA, Bhattacharjee MB, Tiziani S, Heffernan TP, Vellano CP, Jones P, Heijnen CJ, Kavelaars A, Marszalek JR, Konopleva M. Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials. Nat Med. 2023 Jan;29(1):115-126. doi: 10.1038/s41591-022-02103-8. Epub 2023 Jan 19.

    PubMed 36658425

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oxidative Phosphorylation Inhibitor IACS-010759, Pharmacodynamic Study and Pharmacokinetic Study in people with Advanced Malignant Solid Neoplasm and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site 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 21 inclusion and 17 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 24 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Incidence of adverse events (time frame: Up to 2 years). The study lists 2 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 NCT03291938, 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 24 Nov 2020.

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