A Phase I Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours
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|ClinicalTrials.gov Identifier: NCT03427073|
Recruitment Status : Terminated (to re-evaluate biomarker strategy for recruitment to Part 2)
First Posted : February 9, 2018
Results First Posted : September 11, 2019
Last Update Posted : September 11, 2019
ALM201/0001 is a Phase I, open-label, dose-escalation study of the safety, tolerability and pharmacokinetics (PK) of ALM201.
Part 1 will be a dose-escalation study. Patients with advanced solid tumours will receive daily doses of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles.
Part 2 will be a dose-expansion of the Maximum Tolerated Dose (MTD) determined in Part 1. Patients with advanced ovarian cancer will be enrolled with the main objective to determine the recommended Phase II dose.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Ovarian Cancer||Drug: ALM201||Phase 1|
ALM201 is a peptide with anti-angiogenic activity in a range of in-vitro and ex-vivo models. ALM201/0001 is a Phase I, multicentre, open-label, dose-escalation study of the safety, tolerability and pharmacokinetics (PK) of ALM201. The study is divided into two parts.
Part 1 will enrol patients with advanced solid tumours. Patients will receive subcutaneous injection of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles. Patients can receive up to 8 cycles of treatment. Enrolment will follow an accelerated dose-escalation schedule until grade 2 drug-related adverse events are observed, at this point the 3+3 enrolment design will be used. There will be at least 1 week stagger between the first and subsequent patients in a new cohort dose. Dose increments will not exceed 100% escalation and will be guided by data generated from previous cycles. The dose and possibly the schedule will be adjusted to determine the Maximum Tolerated Dose (MTD).
Part 2 will enrol patients with advanced ovarian cancer whose tumour has a proangiogenic profile as assessed by an angiogenesis gene signature biomarker. Patients will receive ALM201 at a dose and schedule established in Part 1.
Patients will undergo safety and tumour assessments as well as blood draws for PK profiling. The safety assessments will involve physical examination, vital signs, biochemistry and haematology laboratory screens as well as immunogenicity testing. Tumour assessments will involve computed tomography (CT) or magnetic resonance imaging (MRI) scans at screening and after every 2 cycles during cycles 1 -8. Patients will be asked to provide consent for access to archived tumour tissue and for fresh biopsies to be taken at pre-dose, tumour response and/or point of disease progression for potential biomarker and pharmacodynamic assessments. PK profiling will be carried out in Cycles 1, 2, 4, 6 and 8.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Open-label Multicentre Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours|
|Actual Study Start Date :||April 27, 2015|
|Actual Primary Completion Date :||March 13, 2017|
|Actual Study Completion Date :||March 13, 2017|
Experimental: Solid tumours
Part 1 - Dose-escalation of ALM201 in patients with advanced solid tumours
Daily dosing of ALM201 on Days 1-5, 8-12 and 15-19 of 21 day cycle. Escalating dose cohorts
Drug: ALM201 administered subcutaneously
Experimental: Ovarian cancer
Part 2 - Dose-expansion of ALM201 Maximum Tolerated Dose (MTD) in patients with advanced ovarian cancer
Daily dosing of ALM201 on Days 1-5, 8-12 and 15-19 of 21 day cycle at the MTD determined in Part 1
Drug: ALM201 administered subcutaneously
- Safety and Tolerability - Evaluation of AEs and DLT [ Time Frame: Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1 ]
All events and suspected dose limiting toxicities (DLTs) were graded according to the CTCAE, version 4.03. A DLT was defined as a Grade 3 or 4 AE that, in the opinion of the CRC, was likely to be related to ALM201 and represented a clinically significant hazard to the patient. Qualifying DLT events were considered to be clinically relevant; e.g. in duration, apparent reversibility, required management, and upon consideration of the patient's medical history and/or concomitant medications. DLT events were also evaluated in terms of what was considered to be an appropriate next escalation step: In the case where the CRC agreed that an escalation step of approximately 33% or lower was merited; the toxicity of concern could be declared a DLT.
In order to be evaluable for DLT assessment, a patient had to receive at least 80% of their scheduled doses (e.g. 12 of the 15), unless this lack of compliance was due to ALM201-related toxicity.
- Tumour Response Assessment - Best Overall Response [ Time Frame: Response assessments were done to assess clinical benefit in the efficacy population overall and at the end of cycles 2, 4 and 6, as applicable ]As this was a Phase 1 study, the extent of efficacy data was expected to be limited. Using RECIST Version 1.1, a summary of clinical benefit from patients with evaluable disease was generated via CT scans: Complete Response (CR) = Disappearance of all target & non-target lesions + normalization of tumor marker; Partial Response (PR) ≥ 30% decrease in the sum of LD of target lesions; Progressive Disease (PD) ≥ 20% increase (& 5mm absolute increase) in sum of LD of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Pharmacokinetics: Tmax [ Time Frame: Tmax was determined in cycles 1, 2, 4 and 6 of treatment ]Tmax was derived from the individual patient plasma concentration versus time profiles of ALM201.
- Pharmacokinetics: AUC 0-t [ Time Frame: AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment ]AUC 0-t was derived from the individual patient plasma concentration versus time profiles of ALM201.
- Pharmacokinetics: Cmax [ Time Frame: Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment ]Cmax was derived from the individual patient plasma concentration of ALM201.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03427073
|Centre for Cancer Research and Cell Biology, Queen's University Belfast|
|Belfast, County Antrim, United Kingdom, BT9 7AB|
|Dept Medical Oncology, The Christie NHS Foundation Trust|
|Manchester, Lancashire, United Kingdom, M20 4BX|
|Freeman Hospital, Northern Centre for Cancer Care, Sir Bobby Robson Cancer Trial research Centre|
|Newcastle, Northumberland, United Kingdom, NE7 7DN|
|Principal Investigator:||Richard Wilson, Professor||Centre for Cancer Research and Cell Biology, Queen's University Belfast|