Trial Outcomes & Findings for Phase I/II Trial of AXL1717 in the Treatment of Recurrent Malignant Astrocytomas (NCT NCT01721577)

Results Overview

To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

8 months

Results posted on

2023-05-22

Participant Flow

One patient was excluded from the study after screening but before treatment and is not considered in this analysis.

Participant milestones

Participant milestones
Measure	AXL1717 400mg BID Started on 400mg BID	AXL1717 300mg BID Started on 300mg BID
Overall Study STARTED	2	7
Overall Study COMPLETED	0	4
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	AXL1717 400mg BID Started on 400mg BID	AXL1717 300mg BID Started on 300mg BID
Overall Study Lack of Efficacy	1	0
Overall Study Death	1	0
Overall Study Dose Escalation to 400mg BID	0	1
Overall Study Adverse Event	0	2

Baseline Characteristics

Phase I/II Trial of AXL1717 in the Treatment of Recurrent Malignant Astrocytomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AXL1717, 400mg Initial Dose n=2 Participants Subjects who started and completed the study on 400mg BID	AXL1717, 300mg Initial Dose n=7 Participants Subjects who started the study on 300mg BID. one subject was escalated to 400mg BID and 2 subjects were de-escalated to 215mg BID	Total n=9 Participants Total of all reporting groups
Age, Continuous	58 Years n=5 Participants	56.2 Years n=7 Participants	56.6 Years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 months

To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.

Outcome measures

Outcome measures
Measure	All Study Participants n=9 Participants All study participants who received different doses of the same formulation of AXL1717.	AXL1717, 300mg Initial Does Subjects who were started on 300mg BID
Phase I - Determine Recommended Phase II Dose	NA MG No dose in the trial met this criteria for establishing a RPTD.	—

PRIMARY outcome

Timeframe: 24 Weeks

Population: Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.

To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 Months

To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.

Outcome measures

Outcome measures
Measure	All Study Participants n=9 Participants All study participants who received different doses of the same formulation of AXL1717.	AXL1717, 300mg Initial Does Subjects who were started on 300mg BID
Phase I - To Identify the Maximum Tolerable Dose	300 MG	—

SECONDARY outcome

Timeframe: 8 months

Population: the data for this outcome measure was not collected and/or analyzed. There is no data to report.

To assess potential molecular markers that might predict optimum response sub-population groups

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 months

Population: None of the secondary outcome measures were collected or analyzed as this study was conducted using the oral suspension of AXL1717 and there is a new formulation of AXL1717 in development (capsule). Decision was made to abandon other analysis or data collections in regards to secondary outcomes.

To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

Population: Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.

To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

Population: Phase II of the study was never initiated. No data was gathered or analyzed.

To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 Months

Population: Phase II of the study was never initiated.

To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 months

Population: Phase II portion of this study was not initiated as the phase 1 piece was not completed fully. This endpoint was not explored and data was not collected or analyzed

To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: 4 months

Number of Participants with Imaging Evidence of Response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).

Outcome measures

Outcome measures
Measure	All Study Participants n=2 Participants All study participants who received different doses of the same formulation of AXL1717.	AXL1717, 300mg Initial Does n=7 Participants Subjects who were started on 300mg BID
Phase I Subjects - Imaging Evidence of Response.	0 Participants	5 Participants

Adverse Events

400mg BID

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

300mg BID

Serious events: 3 serious events

Other events: 1 other events

Deaths: 0 deaths

215mg BID

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	400mg BID n=3 participants at risk Subjects on 400mg BID of AXL1717	300mg BID n=7 participants at risk Subjects on 300mg BID of AXL1717	215mg BID n=2 participants at risk Subjects on 215mg BID of AXL1717
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/7 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/2 • information was collected for each subject while on study (~some were up to 1 year)
Blood and lymphatic system disorders Neutropenia	66.7% 2/3 • Number of events 2 • information was collected for each subject while on study (~some were up to 1 year)	42.9% 3/7 • Number of events 3 • information was collected for each subject while on study (~some were up to 1 year)	50.0% 1/2 • Number of events 1 • information was collected for each subject while on study (~some were up to 1 year)
Blood and lymphatic system disorders Thrombocytopenia	66.7% 2/3 • Number of events 2 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/7 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/2 • information was collected for each subject while on study (~some were up to 1 year)
Vascular disorders Sepsis	33.3% 1/3 • Number of events 1 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/7 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/2 • information was collected for each subject while on study (~some were up to 1 year)

Other adverse events

Other adverse events
Measure	400mg BID n=3 participants at risk Subjects on 400mg BID of AXL1717	300mg BID n=7 participants at risk Subjects on 300mg BID of AXL1717	215mg BID n=2 participants at risk Subjects on 215mg BID of AXL1717
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/7 • information was collected for each subject while on study (~some were up to 1 year)	50.0% 1/2 • Number of events 1 • information was collected for each subject while on study (~some were up to 1 year)
Nervous system disorders Paresthesias	0.00% 0/3 • information was collected for each subject while on study (~some were up to 1 year)	14.3% 1/7 • Number of events 1 • information was collected for each subject while on study (~some were up to 1 year)	0.00% 0/2 • information was collected for each subject while on study (~some were up to 1 year)

Additional Information

Crista Brawley

Rush University Medical Center

Phone: 312-563-2312

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee I am not privvy to all the agreements that exist. But the original PI left the institution where this study was conducted, and he left with a separation agreement in place. I (Crista Brawley) am named in that agreement. Please direct questions to Dr. Robert Aiken.
Publication restrictions are in place

Restriction type: OTHER