Solid TumorsPhase 1NCT03427073
A Phase I Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours
A Phase 1 study testing ALM201 in people with Solid Tumors and Ovarian Cancer, run by Almac Discovery at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Solid Tumors, Ovarian Cancer
- What is being tested?
- ALM201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 27 Apr 2015to 13 Mar 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Part 1 Specific Inclusion Criterion
- Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available or felt likely to be of limited efficacy and in whom a rationale for use of an anti-angiogenic treatment approach exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated
- Part 2 Specific Inclusion Criterion
- Patients with advanced ovarian cancer, who are intolerant of or whose tumour is resistant to platinums and who have failed to respond to, or have relapsed following, standard therapy and whose tumour has a proangiogenic profile as assessed by the angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is allowed if tolerated.
- General Inclusion Criteria for all Patients
- Measurable or evaluable disease.
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- Recovery from previous treatment to baseline or CTCAE ≤ Grade 1, as determined by CTCAE v4.03 criteria (Appendix B), of reversible toxicities related to prior treatment, with the exception of alopecia, lymphopenia, other non-clinically significant adverse events; recovery from previous radiotherapy other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity; complete recovery from surgery other than stable < Grade 2 toxicity.
- ECOG Performance Status (PS) of 0 or 1.
- Acceptable haematological, renal and hepatic
- Women must have either a negative pregnancy test prior to first study drug administration or be post menopausal. Male and female patients of childbearing potential must use appropriate methods birth control.
- Patients must give written informed consent and understand the requirements of the study
Who cannot join
- For all Patients
- History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events.
- Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography.
- Patents has received:
- any chemotherapy regimens (including investigational agents) with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle 1, Day 1, or received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of Cycle 1, Day 1.
- radiotherapy, immunotherapy or biological agents (includes investigational agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.
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- Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours.
- Cancer with leptomeningeal involvement.
- On therapeutic anti-coagulation (aspirin dosing ≤100 mg per oral (PO) daily allowed).
- Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumour was treated with curative intent more than 2 years prior to study entry.
- Active cardiac condition or history of significant cardiac condition. Known human immunodeficiency virus positivity.
- Active hepatitis B or C or other active liver disease (other than malignancy).
- Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
- Any evidence of severe or uncontrolled systemic conditions or any other issues which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Centre for Cancer Research and Cell Biology, Queen's University Belfast
Belfast, County Antrim, BT9 7AB
Dept Medical Oncology, The Christie NHS Foundation Trust
Manchester, Lancashire, M20 4BX
Freeman Hospital, Northern Centre for Cancer Care, Sir Bobby Robson Cancer Trial research Centre
Newcastle, Northumberland, NE7 7DN
About this study
Official title: A Phase I Open-label Multicentre Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours
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.
Read the detailed description
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.
- Conditions
- Solid Tumors, Ovarian Cancer
- Being tested
- ALM201
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALM201Drug
Drug: ALM201 administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Solid tumours | Experimental | 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 Receives: Drug: ALM201 |
| Ovarian cancer | Experimental | 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 Receives: Drug: ALM201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability - Evaluation of AEs and DLT
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.
Measured: Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1
Secondary outcomes (4)
Tumour Response Assessment - Best Overall Response
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.
Measured: 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
Pharmacokinetics: Tmax
Tmax was derived from the individual patient plasma concentration versus time profiles of ALM201.
Measured: Tmax was determined in cycles 1, 2, 4 and 6 of treatment
Pharmacokinetics: AUC 0-t
AUC 0-t was derived from the individual patient plasma concentration versus time profiles of ALM201.
Measured: AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment
Pharmacokinetics: Cmax
Cmax was derived from the individual patient plasma concentration of ALM201.
Measured: Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2018
- Study start27 Apr 2015
- Primary completion13 Mar 2017
- Study completion13 Mar 2017
Why it stopped: to re-evaluate biomarker strategy for recruitment to Part 2
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorsStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Almac Discovery
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Wilson, Professor, Principal investigator, Centre for Cancer Research and Cell Biology, Queen's University Belfast
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03427073
- Sponsor's protocol ID
- ALM201/0001
- Status last verified
- Aug 2019
- First submitted
- 5 Mar 2015
- Last updated
- 11 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label Multicentre Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours
- ClinicalTrials.gov ID
- NCT03427073
- Acronym / sponsor ID
- ALM201/0001
- Conditions
- Solid Tumors, Ovarian Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: to re-evaluate biomarker strategy for recruitment to Part 2
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Almac DiscoveryIndustry (pharma, biotech, devices)
- Study start
- 27 Apr 2015 (actual)
- Primary completion
- 13 Mar 2017 (actual)
- Study completion
- 13 Mar 2017 (actual)
- First posted
- 9 Feb 2018 (actual)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Solid tumours | Experimental | Drug: ALM201Part 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 |
| Ovarian cancer | Experimental | Drug: ALM201Part 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 |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Part 1 Specific Inclusion Criterion
- Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available or felt likely to be of limited efficacy and in whom a rationale for use of an anti-angiogenic treatment approach exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated
- Part 2 Specific Inclusion Criterion
- Patients with advanced ovarian cancer, who are intolerant of or whose tumour is resistant to platinums and who have failed to respond to, or have relapsed following, standard therapy and whose tumour has a proangiogenic profile as assessed by the angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is allowed if tolerated.
- General Inclusion Criteria for all Patients
Key exclusion criteria (14 listed)
- For all Patients
- History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events.
- Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography.
- Patents has received:
- Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALM201Drug: ALM201 administered subcutaneously | Drug | Ovarian cancer, Solid tumours |
Primary outcome
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.
4 secondary outcomes
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
Pharmacokinetics: Tmax
Time frame: Tmax was determined in cycles 1, 2, 4 and 6 of treatment
Pharmacokinetics: AUC 0-t
Time frame: AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment
Pharmacokinetics: Cmax
Time frame: Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Wilson, Professor principal investigator
Centre for Cancer Research and Cell Biology, Queen's University Belfast
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALM201 in people with Solid Tumors and Ovarian Cancer, run by Almac Discovery at 3 sites in United Kingdom.
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 11 inclusion and 14 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: stopped early, as of the sponsor's last update on 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Sep 2019.