CancerPhase 1AP1001NCT00437736
A Phase I Dose Finding Study of APO010 in Patients With Solid Tumors
A Phase 1 study testing APO010 in people with Cancer, run by Valerio Therapeutics at 2 sites in Switzerland.
Trial summary
Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week. It will be the first time this agent will be administered to humans. At lower dose levels, the first cycle duration is 7 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- APO010
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesSwitzerland
- Study dates
- Feb 2007to May 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological/cytological diagnosis of non-resectable solid tumors for which therapy of proven efficacy does not exist or is no longer effective.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
- Ongoing toxicity associated with prior anticancer therapy ≤Grade 1 (NCI-CTCAE v.3.0).
- No more than 3 prior chemotherapy lines for advanced disease (not including neo/adjuvant chemotherapy; reintroduced chemotherapy is considered only 1 line, e.g. platinum reintroduction in ovarian cancer). Exceptions must to be discussed with, and agreed by the Co-ordinating Investigator.
- Adequate hematological, liver and renal function, e.g.:
- Hemoglobin ≥9 mg/dl; Absolute Neutrophil Count (ANC) ≥1.5x109/l; platelets ≥100x109/l; normal coagulation factors (INR, PTT, PT).
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- Serum bilirubin ≤upper normal limit (UNL); ALT, AST ≤ UNL but ≤ 2.5 x UNL in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ UNL or ≤1.5 x UNL of in case liver metastases; albumin within normal limits.
- Creatinine ≤1.5 mg/dl (≤133µmole/l) or calculated creatinine clearance ≥60 ml/min.
- Life expectancy of at least 3 months.
- Capability of understanding the nature of the trial and giving written informed consent.
Who cannot join
- Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy.
- More than 30% liver parenchyma involvement assessed by computed tomography (CT) scan.
- History of hypersensitivity to preparations containing human albumin, and to intravenously administered proteins/peptides/antibodies.
- Active infection.
- Presence of cirrhosis with abnormal liver function test or chronic viral hepatitis.
- Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder.
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- Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
- Symptomatic brain metastases, primary brain tumors or leptomeningeal disease.
- Pregnancy or lactation, or unwillingness to use adequate method of birth control
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
Oncology Institute of Southern Switzerland, Hospital of Bellinzona
Bellinzona, 6500
Multidisciplinary Oncology Center, Cantonal University Hospital of Vaud
Lausanne, 1011
About this study
Official title: Phase I Dose Finding and Pharmacokinetic Study of Intravenous APO010, a Recombinant Form of Human Fas Ligand, in Patients With Solid Tumors
Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week. It will be the first time this agent will be administered to humans. At lower dose levels, the first cycle duration is 7 weeks. In subsequent cycles, APO010 is administered as 4 weekly doses followed by a two-week drug rest, cycle duration is 6 weeks. Based on preclinical studies of APO010 may cause liver toxicity and a drop in platelets, that recover within 5 days. The main aim of the study is to identify the recommended dose of APO010 for future clinical studies of APO010.
Read the detailed description
Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week in patients with solid tumors, for whom therapy of proven efficacy does not exist or is no longer effective. The dose-escalations will follow a classical Fibonacci schedule, meaning at least three patient per dose-level, prior to further escalation. The dose-level assignment and patient registration is centralized by SENDO-Switzerland \& Milan offices.
APO010, Apoxis' proprietary humanized recombinant mega-Fas-ligand, is a novel "First in class" investigational anticancer agent. APO010 is a protein that by specific binding to its cognate Fas receptor on the cell surface induces apoptosis (programmed cell death). This is called the extrinsic apoptotic pathway of cells. APO010 has shown to exert anticancer activity in vitro and in animal models carrying a human xenograft of a variety of cancers, including malignancies such as multiple myeloma, non-small cell lung cancer (NSCLC), ovarian cancer. Its activity is cell cycle independent, it does not cross react with known multi-drug resistance mechanism (MDR) and appears to be synergistic with a variety of commonly used anticancer drugs. Hence, APO010 may an attractive candidate for combination anticancer therapy and may be a effective drug in overcoming MDR.
In this study the starting dose is 2.5 microgram/m2. Normally 1/6 of the No-observed-adverse-effect level (NOAEL) dose-level in monkeys would be chosen as the first dose-level, however it has been decided to start at 25% of that dose-level. Across species (mice, rats and Cynomolgus monkeys) the rise in transaminases and drop in platelets occurred at 30 microgram/m2. The Nadir of these toxicities occurred within 6 hours and full recovery at day 5 after the bolus injection.
At the first occurrence of non-reversible (within 1 week) Common Toxicity Criteria (CTC) v3.0 Grade 2 liver function toxicity (Aspartate transaminase (AST)/Alanine transaminase (ALT) or alkaline phosphatase), i.e. Dose Limiting Toxicity (DLT), the patient accrual will be placed on hold until recovery and the subsequent timing of patient accrual to the existing and subsequent cohorts will be re-defined by the sponsor, the principal investigators and SENDO.
Pharmacokinetic assessments will be carried out in all patients during the first, and in consenting patients during the second cycles of treatment.
Assessment for immunogenicity (binding and/or neutralizing antibodies against APO010 will be carried out in all patients in all cycles of treatment before each dose and 2 weeks after the final dose.
- Conditions
- Cancer
- Being tested
- APO010
- Keywords
- solid tumor, phase I study, dose-escalation
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APO010Drug
APO010 starting at 2.5 µg/m² IV on D1, D15, D22 and D29 followed by a two-week drug rest.
| Study group | Role | What they receive |
|---|---|---|
| Single arm dose escalation | Experimental | Not described Receives: Drug: APO010 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine of the maximum tolerated dose (MTD), based upon first cycle APO010-related DLT in patients with solid tumors.
Measured: 3 months
Secondary outcomes (4)
A description of the frequency and severity of adverse events (AE) based on the NCI-CTC AE v.3.0.
Measured: 3 months
A description of the local toxicity at site of administration by route of administration based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE v.3.0); the intervention required and by photographic record.
Measured: 3 months
A definition of the proportion of patients with neutralizing antibodies against APO010.
Measured: 3 months
A description of any objective tumor response based on modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionNov 2008
- Study completionMay 2009
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cristiana Sessa, Prof, MD, Principal investigator, Oncology Institute of Southern Switzerland, Bellinzona Hospital, 6500 Bellinzona, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00437736
- Sponsor's protocol ID
- AP1001
- Other IDs
- S065APO01
- Acronym
- AP1001
- Status last verified
- Sep 2015
- First submitted
- 20 Feb 2007
- Last updated
- 17 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Finding and Pharmacokinetic Study of Intravenous APO010, a Recombinant Form of Human Fas Ligand, in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT00437736
- Acronym / sponsor ID
- AP1001 / AP1001
- Conditions
- Cancer
- Keywords
- solid tumor, phase I study, dose-escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 21 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week. It will be the first time this agent will be administered to humans. At lower dose levels, the first cycle duration is 7 weeks. In subsequent cycles, APO010 is administered as 4 weekly doses followed by a two-week drug rest, cycle duration is 6 weeks. Based on preclinical studies of APO010 may cause liver toxicity and a drop in platelets, that recover within 5 days. The main aim of the study is to identify the recommended dose of APO010 for future clinical studies of APO010.
Detailed description
Two-centre, open label, uncontrolled, dose-finding phase I study, to determine the safety and tolerability of APO010 administered by intravenous bolus injection once per week in patients with solid tumors, for whom therapy of proven efficacy does not exist or is no longer effective. The dose-escalations will follow a classical Fibonacci schedule, meaning at least three patient per dose-level, prior to further escalation. The dose-level assignment and patient registration is centralized by SENDO-Switzerland \& Milan offices.
APO010, Apoxis' proprietary humanized recombinant mega-Fas-ligand, is a novel "First in class" investigational anticancer agent. APO010 is a protein that by specific binding to its cognate Fas receptor on the cell surface induces apoptosis (programmed cell death). This is called the extrinsic apoptotic pathway of cells. APO010 has shown to exert anticancer activity in vitro and in animal models carrying a human xenograft of a variety of cancers, including malignancies such as multiple myeloma, non-small cell lung cancer (NSCLC), ovarian cancer. Its activity is cell cycle independent, it does not cross react with known multi-drug resistance mechanism (MDR) and appears to be synergistic with a variety of commonly used anticancer drugs. Hence, APO010 may an attractive candidate for combination anticancer therapy and may be a effective drug in overcoming MDR.
In this study the starting dose is 2.5 microgram/m2. Normally 1/6 of the No-observed-adverse-effect level (NOAEL) dose-level in monkeys would be chosen as the first dose-level, however it has been decided to start at 25% of that dose-level. Across species (mice, rats and Cynomolgus monkeys) the rise in transaminases and drop in platelets occurred at 30 microgram/m2. The Nadir of these toxicities occurred within 6 hours and full recovery at day 5 after the bolus injection.
At the first occurrence of non-reversible (within 1 week) Common Toxicity Criteria (CTC) v3.0 Grade 2 liver function toxicity (Aspartate transaminase (AST)/Alanine transaminase (ALT) or alkaline phosphatase), i.e. Dose Limiting Toxicity (DLT), the patient accrual will be placed on hold until recovery and the subsequent timing of patient accrual to the existing and subsequent cohorts will be re-defined by the sponsor, the principal investigators and SENDO.
Pharmacokinetic assessments will be carried out in all patients during the first, and in consenting patients during the second cycles of treatment.
Assessment for immunogenicity (binding and/or neutralizing antibodies against APO010 will be carried out in all patients in all cycles of treatment before each dose and 2 weeks after the final dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm dose escalation | Experimental | Drug: APO010 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histological/cytological diagnosis of non-resectable solid tumors for which therapy of proven efficacy does not exist or is no longer effective.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
- Ongoing toxicity associated with prior anticancer therapy ≤Grade 1 (NCI-CTCAE v.3.0).
- No more than 3 prior chemotherapy lines for advanced disease (not including neo/adjuvant chemotherapy; reintroduced chemotherapy is considered only 1 line, e.g. platinum reintroduction in ovarian cancer). Exceptions must to be discussed with, and agreed by the Co-ordinating Investigator.
- Adequate hematological, liver and renal function, e.g.:
Key exclusion criteria (9 listed)
- Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy.
- More than 30% liver parenchyma involvement assessed by computed tomography (CT) scan.
- History of hypersensitivity to preparations containing human albumin, and to intravenously administered proteins/peptides/antibodies.
- Active infection.
- Presence of cirrhosis with abnormal liver function test or chronic viral hepatitis.
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 |
|---|---|---|
| APO010APO010 starting at 2.5 µg/m² IV on D1, D15, D22 and D29 followed by a two-week drug rest. | Drug | Single arm dose escalation |
Primary outcome
To determine of the maximum tolerated dose (MTD), based upon first cycle APO010-related DLT in patients with solid tumors.
Time frame: 3 months
4 secondary outcomes
A description of the frequency and severity of adverse events (AE) based on the NCI-CTC AE v.3.0.
Time frame: 3 months
A description of the local toxicity at site of administration by route of administration based on the NCI-Common Terminology Criteria for Adverse Events (NCI-CTCAE v.3.0); the intervention required and by photographic record.
Time frame: 3 months
A definition of the proportion of patients with neutralizing antibodies against APO010.
Time frame: 3 months
A description of any objective tumor response based on modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2015.
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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.
Cristiana Sessa, Prof, MD principal investigator
Oncology Institute of Southern Switzerland, Bellinzona Hospital, 6500 Bellinzona, Switzerland
2 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 APO010 in people with Cancer, run by Valerio Therapeutics at 2 sites in Switzerland.
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 10 inclusion and 9 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: finished, as of the sponsor's last update on 17 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine of the maximum tolerated dose (MTD), based upon first cycle APO010-related DLT in patients with solid tumors. (time frame: 3 months). 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 17 Sep 2015.