CancerPhase 1/2NCT05500508

Oral AMXT 1501 Dicaprate in Combination With IV DFMO

A Phase 1/2 study testing AMXT1501 and DFMO in people with Cancer and Solid Tumor, run by Aminex Therapeutics, Inc. at 7 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

A Phase 1B/2A study will be conducted to establish safety and dose level of AMXT 1501 dicaprate in combination with IV DFMO, in cancer patients. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Cancer, Solid Tumor, Solid Carcinoma
What is being tested?: AMXT1501 and DFMO
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 7 sitesin 2 countries
Study dates: 29 Nov 2022to 12 Dec 2024
Phase: Phase 1/2

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 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

IMPORTANT NOTE- Younger 12-17 year old patients are also eligible for this study if they meet the noted DIPG or DMG criteria noted below, which is separate from Patient Diagnosed with Advanced Solid Tumors.
Patients will be eligible for study participation only if they meet ALL the inclusion criteria applicable to their diagnosis.
Understand and sign written IRB-approved informed consent form and be willing to comply with all study procedures.
Diagnosed with unresectable, locally advanced, or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed. Planned tumor types for evaluation include:
Platinum resistant ovarian cancer (including - primary peritoneal cancer and fallopian tube cancer)
Breast cancer

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Papillary thyroid cancer
Head and neck cancer
Gastric cancer
Non-small cell lung cancer (NSCLC)
Mesothelioma: Pleural and peritoneal
Esophageal
Endometrial cancer
Cervical
Melanoma
Colorectal cancers (colon, rectal)
Grade 4 Gliomas (including both IDH WT and IDH-mutant astrocytoma)
Must be ≥18 years of age.
Histologically or cytologically documented disease.
Has evaluable or measurable disease by RECIST v1.1 or mRECIST criteria.
o For patients with Grade 4 glioma, has evaluable or measurable disease by RANO (Appendix 5).
Provide tumor tissue from biopsy taken during Screening period.
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
INCLUSION FOR PATIENTS DIAGNOSED WITH DIPG OR DMG Patients must also meet other generally noted criteria as noted within the protocol
For patients <18 years of age, the parents or legal guardians must understand and sign the written IRB-approved informed consent form (ICF). The patient, if able, must understand and sign the IRB-approved consent (assent) and be willing to comply with all study procedures.
o For patients ≥18 years of age, the patient must understand and sign written IRB-approved ICF and be willing to comply with all study procedures.
Diagnosed with DIPG or DMG.
o Any anatomic site of origin is acceptable.
Must be ≥12 years of age and >40 kg in body weight.
Radiologically documented disease.
(a) - Patient with refractory or progressive DIPG or DMG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation.
(b) - Patients with brainstem tumors that do not meet radiographic criteria or are not considered to be typical DIPG or DMG will be eligible if the tumors have been biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, H3 K27M-mutant DMG).
Has evaluable or measurable disease by RANO or RAPNO criteria.
o Has evaluable or measurable disease by RANO (for adults) or RAPNO (for children
Provide cerebrospinal fluid (CSF) sample. Patients with pontine lesions for whom a radiological diagnosis of DIPG, or DMG is made will be eligible without a CSF sample, although CSF sample is strongly encouraged.
Performance score:
(a) Patients >16 years of age, Karnofsky score ≥50%.
(b) Patients ≥12 and ≤16 years of age, Lansky ≥50%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
INCLUSION FOR ALL PATIENTS All patients are required to meet these inclusion exclusion criteria to be considered eligible for the study
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy: The following minimum periods from treatment apply:
(a) Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
(b) Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting growth factor.
(c) Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
(d) Immunotherapy: At least 42 days after the completion of any type of vaccination.
(e) Monoclonal antibodies: >21 days must have elapsed from the infusion of last dose of antibody and toxicity related to antibody therapy must be recovered to Grade ≤1.
(f) Radiation therapy: Patients must have had their last fraction of craniospinal or focal irradiation a minimum of 8-12 weeks prior to enrollment.
(g) Stem cell transplant: Patients must be ≥3 months since autologous stem cell transplant. Patients who received allogenic stem cell transplant or solid organ transplant are not eligible for study.
Patient is able to take oral medications and willing to use an at-home infusion pump.
Must have adequate bone marrow and renal/hepatic function at the screening and baseline visits, defined as:
(a) Absolute neutrophil count (ANC) ≥1.5×109/L without granulocyte colony-stimulating factor (G-CSF) support within 7 days
(b) Platelet ≥100×109/L, without transfusion within 7 days
(c) Hemoglobin ≥9 g/dL, without transfusion support within 7 days
(d) Activated partial thromboplastin time/ partial thromboplastin time (aPTT/PTT) ≤1.5×ULN.
(e) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (if liver metastases are present, then ≤5×ULN is allowed).
(f) Total serum bilirubin ≤1.5×ULN, (except for patients with known Gilbert's Syndrome in whom ≤3×ULN is permitted).
(g) The patient is clinically euthyroid.
(h) Renal: Serum creatinine <1.5×ULN or creatinine clearance ≥60 mL/min/1.73 m2 for patients with serum creatinine levels >1.5×ULN.
(i) Any Grade 3 or higher lab abnormalities should be discussed and approved by the Medical Monitor prior to enrollment (even if not considered clinically significant).
Active secondary malignancies will not be allowed, with the exception of:
(a) Adequately treated basal cell carcinoma, SCC of the skin, or in situ cervical cancer;
(b) Adequately treated Stage 1 cancer from which the subject is currently in remission and has been in remission for ≥2 years;
(c) Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL, or
(d) Any other cancer from which the patient has been disease-free for ≥3 years.
Patient compliance and geographic proximity (as determined by the Principal Investigator [PI]) to allow adequate follow-up.
Both male and female patients must be willing to consent to using highly effective contraception prior to study entry, while on treatment, and at least 3 months thereafter

Who cannot join

Patients will not be eligible for study participation if they meet ANY of the exclusion criteria.
Please note different criteria for patients with Advanced Solid Tumors (adults) vs patients with DIPG or DMG (pediatric)
EXCLUSION FOR PATIENTS DIAGNOSED WITH ADVANCED SOLID TUMOR(S)
Have a seizure disorder where >1 seizure has occurred within the last year.
Patient with treated (surgically excised or irradiated) with stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and baseline brain CT with contrast or magnetic resonance imaging (MRI) within 2 weeks of initiation of study drug is negative for new brain metastases. Patients with stable brain metastases must not require therapy with corticosteroids.
Treatment with radiation therapy, surgery, chemotherapy, or immunotherapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C). Limited prior palliative radiation may be permissible no less than 2 weeks prior to C1D1 with approval from the Medical Monitor.

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Patients with seizure disorders may be enrolled if seizures are well-controlled, defined as no increase in seizure frequency in the prior 7 days.
Anticonvulsants should be used as clinically indicated.
The use of enzyme inducing anticonvulsants is not permitted.
Patients with treated (surgically excised or irradiated) stable brain metastases are eligible as long as the treatment was at least 8 to 12 weeks prior to initiation of study drug and baseline brain CT with contrast or MRI within 2 weeks of initiation of study drug is negative for new brain metastases. Patients with brain metastases or who have Grade 4 glioma receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
Have clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 3 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, or history of cerebrovascular accident [CVA]) within 6 months of enrollment.
History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful.
Screening QTcF interval >480 ms is excluded. In the event that a single QTcF is >480 ms, the patient may enroll if the average QTcF for the 3 ECGs is <480 ms.
For patients with an intraventricular conduction delay (QRS interval >120 ms), the JTc interval may be used in place of the QTcF with Sponsor approval. The JTc must be <340 ms if JTc is used in place of the QTcF.
Patients with an intraventricular delay due to a left bundle branch block are excluded.
Note: QTcF prolongation due to pacemaker may enroll if the JTc is normal
Had major surgery, other than diagnostic surgery, within 4-weeks prior to Day 1.
Have active bacterial, viral, or fungal infections requiring systemic therapy.
Women who are pregnant or lactating: NOTE: Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 1 week prior to treatment.
Women not OCBP is defined as
(i) Postmenopausal with >1 year since last menses
-- (a) If <65 years old, follicle-stimulating hormone (FSH) >40 mIU/mL.
-- (b) If ≥65 years old and not on hormone replacement therapy (HRT), FSH >30 mIU/mL.
-- (c)If ≥65 years old and on HRT, the FSH requirement is not applicable. Postmenopausal females on HRT will be allowed if HRT has been stable for ≥6 months prior to dosing of study drug(s).
Written medical documentation of being sterilized (e.g., hysterectomy, double oophorectomy, bilateral salpingectomy) with the procedure performed ≥6 months prior to dosing study drug(s).
Note: Tubal ligation is not considered a form of permanent sterilization.
Patients may not have any unresolved toxicity >Grade 1 from previous anticancer therapy, except for stable chronic toxicities that are not expected to resolve (i.e., peripheral neuropathy, alopecia, etc.). Patients who have an ongoing requirement for thyroid replacement therapy from prior exposure to a checkpoint inhibitor but who are clinically euthyroid are permitted.
Have an unwillingness or inability to comply with procedures required in this protocol.
Current active liver disease from any cause, including hepatitis A (hepatitis A virus immunoglobulin M [Hep A IgM] positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Patients with HCV with undetectable virus after treatment are eligible. Patients with a prior history of HBV are eligible if quantitative polymerase chain reaction (PCR) for HBV DNA is negative. Note that elevated levels of biotin may interfere with viral serology testing.
Have a serious nonmalignant disease that, in the opinion of the Investigator or the Medical Monitor, could compromise protocol objectives.
Patients who are currently receiving any other investigational agent or who have received an investigational agent within the last 28 days, with the exception of any patient who participated in Study AMXT1501-101A.
Known GI disease or procedure that could interfere with the absorption of study drug, including inability to swallow whole capsules or conditions that may interfere with absorption. The Medical Monitor should be contacted for any questions regarding this exclusion criterion.
Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation.
Use of luteinizing hormone-releasing hormone (LHRH) agonist / antagonists are not permitted.
Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 µg (NIH-ODS 2020; Section 5.9.2.1). NOTE: Patients who switch from a high dose to a dose of ≤30 µg/day are eligible for study entry.
Infection with human immunodeficiency virus (HIV)-1 or HIV-2. o Exception: Patients with well-controlled HIV (e.g., CD4 >350/mm3 and undetectable viral load) are eligible.

Trial locations and contacts

7 sites in 2 countries.

Country

City, postcode or hospital

7 sites in 2 countries

United States6 sites

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic - Florida
Jacksonville, Florida, 32224
Mayo Clinic - Arizona
Phoenix, Arizona, 85054
Mayo Clinic - Minnesota
Rochester, Minnesota, 55905
Fred Hutch Cancer Center - Seattle Cancer Care Alliance
Seattle, Washington, 98109

Other trials in United States

Australia1 site

Kids Cancer Centre
Sydney, New South Wales

Other trials in Australia

About this study

Official title: A Phase 1B/2A Study of the Safety, Tolerability and Initial Efficacy of Oral AMXT 1501 Dicaprate and Intravenous Difluoromethylornithine (DFMO) in Patients With Cancer

A Phase 1B/2A study will be conducted to establish safety and dose level of AMXT 1501 dicaprate in combination with IV DFMO, in cancer patients.

Read the detailed description

The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with IV DFMO in patients with advanced solid tumors, or DIPG/DMG. Secondary objectives include characterization of plasma pharmacokinetics (PK), pharmacodynamic (PD), and other biomarker efficacy assessments of the impact of AMXT 1501 in combination with IV DFMO on polyamine uptake by circulating lymphocytes (blood cells). To these aims, the study will evaluate the safety, PK, PD, and other biomarker efficacy profiles of orally-administered AMXT 1501 and IV DFMO. Approximately, 56 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and IV DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.

Conditions: Cancer, Solid Tumor, Solid Carcinoma, Advanced Cancer, DIPG Brain Tumor, Ovary Cancer
Being tested: AMXT1501, DFMO
Keywords: DFMO IV, AMXT 1501, DFMO
Medical subject headings: Neoplasms, Diffuse Intrinsic Pontine Glioma, Ovarian Neoplasms, Breast Neoplasms, Thyroid Cancer, Papillary, Head and Neck Neoplasms, Stomach Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

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

AMXT1501Drug
AMXT 1501 dicaprate is D-lys(palmitoyl)-spermine dicaprate salt in 200 mg (free base content) enterically-coated capsules
DFMODrug
Also called difluoromethyl ornithine monohydrochloride
DFMO is DL-2-(difluoromethyl) ornithine monohydrochloride monohydrate provided as a 200 mg/mL aqueous solution in 20 mL vials.

Study groups in NCT05500508
Study group	Role	What they receive
Escalation	Experimental	Dose escalation of DFMO with AMXT1501 fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 1200mg total daily dose (200 mg capsules; 3 capsules in morning; 3 capsules in evening) along with IV DFMO administered in continuous infusion at 2mL/hr over a 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per cohort. Receives: Drug: AMXT1501; Drug: DFMO
Expansion	Experimental	The expansion cohort will include up to 40 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by AMXT1501-101A study to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity. Receives: Drug: AMXT1501; Drug: DFMO

What is being measured

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

Determine DLTs and RP2Ds in AMXT 1501 in combination with IV DFMO
Indicate Number of patients with DLTs in AMXT1501 in combination with IV DFMO in patients with advanced cancer to determine the RP2D within the duration of the dose escalation period of the study as defined by the DLT definition of the protocol from baseline to end of Cycle 1
Measured: 1 year
Determine safety and tolerability of AMXT1501 in combination with IV DFMO
To evaluate the safety and tolerability of AMXT1501 and IV DFMO combination in patients through collecting the number of patients with Treatment Related Adverse Events that occur in patients from first dose, AEs assessed by CTCAEv5.0
Measured: 1 year

Secondary outcomes (5)

Determine the PK using AUC of AMXT 1501 and IV DFMO
To evaluate the pharmacokinetics (PK) of AMXT 1501 in combination with IV DFMO in patients
Measured: 6 months
Determine the PK using Cmax of AMXT 1501 and IV DFMO
To evaluate the pharmacokinetics (PK) of AMXT 1501 and IV DFMO
Measured: 6 months
Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1
To characterize Investigator defined Overall Response Rate (ORR) using RECIST v1.1 response criteria.
Measured: 6 months
Characterize investigator defined Duration of Response (DOR)
To characterize Investigator defined Duration of Response (DOR), using RECIST v1.1 response criteria and length of time (in days) from last study drug administration to time patient has progressive disease.
Measured: 6 months
Characterize AMXT1501 and IV DFMO on the expression of immune related gene signatures
Evaluate the effects of AMXT1501 and IV DFMO on the expression of immune related gene signatures, immune cell phenotype by IHC, AMXT1501 and DFMO drug levels impact on polyamine levels
Measured: 1 year

Timeline

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

29 Nov 202212 Dec 2024

First posted15 Aug 2022
Study start29 Nov 2022
Primary completion12 Dec 2024
Study completion12 Dec 2024

Why it stopped: Required re-formulation of DFMO from IV to capsule to maintain safety

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05500508
Sponsor's protocol ID: AMXT1501-102
Status last verified: Dec 2024
First submitted: 10 Aug 2022
Last updated: 24 Dec 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No