Oral AMXT 1501 Dicaprate in Combination With DFMO

Phase 1

Completed

• Conditions: Advanced Cancer; Cancer; Solid Carcinoma; Solid Tumor
• Interventions: Drug: AMXT1501; Drug: DFMO

• Registration Number: NCT03536728
• Lead Sponsor: Aminex Therapeutics, Inc.

Brief Summary

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

Detailed Description

The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with DFMO in patients with advanced solid tumors. Secondary objectives include characterization of plasma pharmacokinetics (PK) of AMXT 1501 as well as pharmacodynamic (PD) assessment of the impact of AMXT 1501 in combination with DFMO on polyamine uptake by circulating lymphocytes (blood cells).

To these aims, the study will evaluate the safety, PK and PD profiles of orally-administered AMXT 1501 and DFMO. Approximately, 52 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.

Study Timeline

• Study First Submitted: 2018-04-04
• Study First Submitted QC: 2018-05-23
• Study First Posted: 2018-05-25
• Study Start: 2018-06-12
• Primary Completion: 2022-12-30
• Study Completion: 2023-04-21
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-23
• Last Update Posted: 2023-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2	DFMO	Dose escalation of DFMO with the Part 1 AMXT1501 RP2D fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be one level below the AMXT 1501 Part 1 RP2D with 500 mg DFMO BID. The morning dose will be given orally of both AMXT1501 and DFMO, in a fasted state. The evening dose of DFMO alone will be given prior to bed-time for 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 Part 2 cohort.
Expansion	DFMO	The expansion cohort will include up to 14 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by Part 2 to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.
Part 1	AMXT1501	Dose escalation of AMXT1501 with a fixed low dose of DFMO will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 80 mg (2 capsules); each capsule contains 40 mg of active drug. The dose will be given orally, once daily, fasted state alone for 14 days, and starting on Day 15 AMXT 1501 80 mg given in combination with fixed low-dose oral DFMO at 250mg 2x per day (BID), for an additional 14 days; for a total 28 days of treatment per cycle. Cycle 2 includes AMXT1501 + DFMO that will be administered for 28 days. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of AMXT1501 alone will increase per Part 1 cohort.
Part 2	AMXT1501	Dose escalation of DFMO with the Part 1 AMXT1501 RP2D fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be one level below the AMXT 1501 Part 1 RP2D with 500 mg DFMO BID. The morning dose will be given orally of both AMXT1501 and DFMO, in a fasted state. The evening dose of DFMO alone will be given prior to bed-time for 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 Part 2 cohort.
Expansion	AMXT1501	The expansion cohort will include up to 14 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by Part 2 to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.
Part 1	DFMO	Dose escalation of AMXT1501 with a fixed low dose of DFMO will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 80 mg (2 capsules); each capsule contains 40 mg of active drug. The dose will be given orally, once daily, fasted state alone for 14 days, and starting on Day 15 AMXT 1501 80 mg given in combination with fixed low-dose oral DFMO at 250mg 2x per day (BID), for an additional 14 days; for a total 28 days of treatment per cycle. Cycle 2 includes AMXT1501 + DFMO that will be administered for 28 days. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of AMXT1501 alone will increase per Part 1 cohort.

Primary Outcome Measures

Name	Time	Method
Determine safety and tolerability of AMXT1501 in combination with DFMO	2 years	To evaluate the safety and tolerability of AMXT1501 and DFMO combination
Determine DLTs and RP2Ds in AMXT 1501 in combination with DFMO	2 years	To evaluate dose-limiting toxicities (DLTs) of AMXT 1501 in combination with DFMO, in patients with advanced cancer and to establish a recommended Phase 2 dose (RP2D)

Secondary Outcome Measures

Name	Time	Method
Determine the PK using AUC of AMXT 1501 and in combination with DFMO	6 months	To evaluate the pharmacokinetics (PK) of AMXT 1501 alone and in combination with DFMO
Determine the PK using Cmax of AMXT 1501 and in combination with DFMO	6 months	To evaluate the pharmacokinetics (PK) of AMXT 1501 alone and in combination with DFMO
Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1	6 months	To characterize Investigator defined Overall Response Rate (ORR) using RECIST v1.1 response criteria.
Characterize investigator defined Duration of Response (DOR)	6 months	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.
Characterize AMXT1501 in combination with DFMO on the expression of immune related gene signatures	1 year	Evaluate the effects of treatment with AMXT1501 in combination with DFMO on the expression of immune related gene signatures, immune cell phenotype by IHC, AMXT1501 and DFMO drug levels impact on polyamine levels

Trial Locations

Locations (4)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Next Oncology - San Antonio; 🇺🇸 San Antonio, Texas, United States

Virginia Cancer Center; 🇺🇸 Fairfax, Virginia, United States

Next Oncology - Austin Midtown; 🇺🇸 Austin, Texas, United States