Advanced Non-Hematologic MalignanciesPhase 1NCT00915278
A Safety Study Of A Monoclonal Antibody Against A5B1 Integrin In Solid Tumors
A Phase 1 study testing PF-04605412 in people with Advanced Non-Hematologic Malignancies, run by Pfizer at 7 sites in 2 countries.
Trial summary
Dose finding study of the MoaB PF-04605412 directed against the alpha5beta1 integrin. Main objective is to define the MTD (maximum tolerated dose) or MAD (maximum administrable dose) in cancer patients pre treated or unresponsive to standard therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Non-Hematologic Malignancies
- What is being tested?
- PF-04605412
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Sep 2009to Jan 2013
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed advanced measurable or evaluable solid tumors unresponsive to currently available therapies, or for which there is no curative therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0 and 1
- Life expectancy more than12 weeks
- Adequate bone marrow, liver and renal function
Who cannot join
- Known brain metastasis
- Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of start of screening procedures
- Major surgical procedure within 4 weeks of start of screening procedures
- Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States4 sites
Pfizer Investigational Site
Nashville, Tennessee, 37232-5536
Pfizer Investigational Site
Nashville, Tennessee, 37232-7610
Pfizer Investigational Site
Nashville, Tennessee, 37232
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19111
United Kingdom3 sites
Pfizer Investigational Site
North Cheam, Surrey, SM3 9DW
Pfizer Investigational Site
Sutton, Surrey, SM2 5PT
Pfizer Investigational Site
Tooting, London, SW17 0QT
About this study
Official title: A Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of The Anti-A5B1 Integrin Monoclonal Antibody PF-04605412 Administered Intravenously To Adult Patients With Advanced Or Metastatic Solid Tumors
Dose finding study of the MoaB PF-04605412 directed against the alpha5beta1 integrin. Main objective is to define the MTD (maximum tolerated dose) or MAD (maximum administrable dose) in cancer patients pre treated or unresponsive to standard therapies.
- Conditions
- Advanced Non-Hematologic Malignancies
- Being tested
- PF-04605412
- Keywords
- Neoplasms, monoclonal antibody, PF-04605412, advanced metastatic solid tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04605412Drug
PF-04605412 will be administered as 2 hr IV infusion every 4 or 2 weeks. Start dose is 7.5 mg. Multiple doses are foreseen. Treatment will continue until intolerable toxicity, progression of disease or patient's refusal
| Study group | Role | What they receive |
|---|---|---|
| PF-04605412 | Experimental | Not described Receives: Drug: PF-04605412 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLT)
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity,any >= Grade 3 adverse event (AE) graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 3.0 without a clear alternative explanation to study treatment relationship occurring during the first 6 weeks of treatment with PF-04605412. DLT was used to determine maximum tolerated dose (MTD) in this study.
Measured: Baseline up to 6 weeks PF-04605412
Secondary outcomes (22)
Maximum Observed Serum Concentration (Cmax)
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the serum concentration time-curve from zero to the last measured concentration (AUClast).
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]
AUC (0 - inf)= Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Serum Decay Half-Life (t1/2)
Serum decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Time to Reach Maximum Observed Serum Concentration (Tmax)
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Systemic Clearance (CL)
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Volume of Distribution at Steady State (Vss)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Measured: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Number of Participants Positive for Anti-PF04605412 Antibodies
Serum samples were analyzed for anti-drug antibodies (ADA) or human anti-human antibodies (HAHA). This was used to evaluate immunogenicity.
Measured: Baseline up to end of treatment
Objective Response - Number of Participants With Objective Response
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Measured: Baseline up to 6 weeks after the first infusion of PF-04605412 (end of Cycle 2) and approximately every 6 weeks thereafter only in the absence of progressive disease
Percent Change in Transfer Constant (Ktrans) From Baseline to Cycle 1 Day 15
Percent change in Ktrans for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from baseline to Cycle 1 day 15 aimed at defining the effect of PF-04605412 on tumor vasculature.
Measured: Screening, and Cycle 1 Day 15
Percent Change in Initial Area Under the Curve (IAUC)
Percent change in the IAUC for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from baseline to Cycle 1 Day 15. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Measured: Screening, and Cycle 1 Day 15
Number of Participants With Tissue Macrophage Infiltration
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against tissue macrophages.
Measured: Predose and postdose
Number of Participants With Integrin Alpha 5 Beta 1 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against integrin alpha 5 beta 1.
Measured: Predose and postdose
Number of Participants With CD68 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies CD68.
Measured: Predose and postdose
Number of Participants With Granzyme B Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Granzyme B.
Measured: Predose and postdose
Number of Participants With CD56 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD56.
Measured: Predose and postdose
Number of Participants With CD16 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD16.
Measured: Predose and postdose
Number of Participants With pFAK Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against pFAK.
Measured: Predose and postdose
Number of Participants With CD31 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD31.
Measured: Predose and postdose
Number of Participants With Caspase 3 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Caspase 3.
Measured: Predose and postdose
Number of Participants With Ki67 Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Ki67.
Measured: Predose and postdose
Number of Participants With Perforin Expression
Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Perforin.
Measured: Predose and postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: The study was terminated on 26 February 2013. Risk-benefit assessment is no longer positive and does not support further development
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 Advanced Non-Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- 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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00915278
- Sponsor's protocol ID
- B1001001
- Status last verified
- Feb 2014
- First submitted
- 3 Jun 2009
- Last updated
- 4 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of The Anti-A5B1 Integrin Monoclonal Antibody PF-04605412 Administered Intravenously To Adult Patients With Advanced Or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00915278
- Acronym / sponsor ID
- B1001001
- Conditions
- Advanced Non-Hematologic Malignancies
- Keywords
- Neoplasms, monoclonal antibody, PF-04605412, advanced metastatic solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated on 26 February 2013. Risk-benefit assessment is no longer positive and does not support further development
- Enrolment
- 33 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 8 Jun 2009 (estimated)
- Results
- Posted 4 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dose finding study of the MoaB PF-04605412 directed against the alpha5beta1 integrin. Main objective is to define the MTD (maximum tolerated dose) or MAD (maximum administrable dose) in cancer patients pre treated or unresponsive to standard therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-04605412 | Experimental | Drug: PF-04605412 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically or cytologically confirmed advanced measurable or evaluable solid tumors unresponsive to currently available therapies, or for which there is no curative therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0 and 1
- Life expectancy more than12 weeks
- Adequate bone marrow, liver and renal function
Key exclusion criteria (4 listed)
- Known brain metastasis
- Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of start of screening procedures
- Major surgical procedure within 4 weeks of start of screening procedures
- Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months
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 |
|---|---|---|
| PF-04605412PF-04605412 will be administered as 2 hr IV infusion every 4 or 2 weeks. Start dose is 7.5 mg. Multiple doses are foreseen. Treatment will continue until intolerable toxicity, progression of disease or patient's refusal | Drug | PF-04605412 |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLT)
Time frame: Baseline up to 6 weeks PF-04605412
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity,any >= Grade 3 adverse event (AE) graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 3.0 without a clear alternative explanation to study treatment relationship occurring during the first 6 weeks of treatment with PF-04605412. DLT was used to determine maximum tolerated dose (MTD) in this study.
22 secondary outcomes
Maximum Observed Serum Concentration (Cmax)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Serum Decay Half-Life (t1/2)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Systemic Clearance (CL)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Volume of Distribution at Steady State (Vss)
Time frame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
Number of Participants Positive for Anti-PF04605412 Antibodies
Time frame: Baseline up to end of treatment
Objective Response - Number of Participants With Objective Response
Time frame: Baseline up to 6 weeks after the first infusion of PF-04605412 (end of Cycle 2) and approximately every 6 weeks thereafter only in the absence of progressive disease
Percent Change in Transfer Constant (Ktrans) From Baseline to Cycle 1 Day 15
Time frame: Screening, and Cycle 1 Day 15
Percent Change in Initial Area Under the Curve (IAUC)
Time frame: Screening, and Cycle 1 Day 15
Number of Participants With Tissue Macrophage Infiltration
Time frame: Predose and postdose
Number of Participants With Integrin Alpha 5 Beta 1 Expression
Time frame: Predose and postdose
Number of Participants With CD68 Expression
Time frame: Predose and postdose
Number of Participants With Granzyme B Expression
Time frame: Predose and postdose
Number of Participants With CD56 Expression
Time frame: Predose and postdose
Number of Participants With CD16 Expression
Time frame: Predose and postdose
Number of Participants With pFAK Expression
Time frame: Predose and postdose
Number of Participants With CD31 Expression
Time frame: Predose and postdose
Number of Participants With Caspase 3 Expression
Time frame: Predose and postdose
Number of Participants With Ki67 Expression
Time frame: Predose and postdose
Number of Participants With Perforin Expression
Time frame: Predose and postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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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.
Pfizer CT.gov Call Center study director
Pfizer
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-04605412 in people with Advanced Non-Hematologic Malignancies, run by Pfizer at 7 sites in 2 countries.
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 4 inclusion and 4 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 4 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, 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 4 Apr 2014). 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?
Number of Participants With Dose-limiting Toxicities (DLT) (time frame: Baseline up to 6 weeks PF-04605412). 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 4 Apr 2014.