First In Human, Phase 1 Study of AG013736 In Patients With Solid Tumors

A Phase 1 study testing AG-013736 in people with Advanced Solid Tumors, run by Pfizer at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of the study was to characterize the safety of investigational agent AG-013736, in patients with solid tumors in this First In Human trial. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors
What is being tested?: AG-013736
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 3 sitesUnited States
Study dates: Nov 2002to Aug 2004
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

Patients with cytologically or histologically confirmed solid tumor(s) and with at least one measurable disease site
Patients with adequate bone marrow, liver and kidney function
Patients with life expectancy of at least 12 weeks

Who cannot join

Patients who have received chemotherapy, immunotherapy, radiotherapy or any investigational agent within 4 weeks of study entry
Patients with have had a major surgical procedure within 4 weeks of study entry

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Pfizer Investigational Site
Houston, Texas, 77030
Pfizer Investigational Site
Madison, Wisconsin, 53792
Pfizer Investigational Site
San Francisco, California, 94115

Other trials in United States

About this study

Official title: Phase I, Open-Label, Multicenter, Dose-Escalation Study Of The Tyrosine Kinase Inhibitor Of VEGFR-2, AG013736, In Patients With Advanced Solid Tumors

The purpose of the study was to characterize the safety of investigational agent AG-013736, in patients with solid tumors in this First In Human trial.

Conditions: Advanced Solid Tumors
Being tested: AG-013736

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AG-013736Drug
Axitinib continuous oral dosing (10 mg once a day, 10 mg twice a day, 20 mg twice a day or 30 mg twice day) in the fed state
AG-013736Drug
Axitinib continuous oral dosing (20 mg twice a day) in the fed state
AG-013736Drug
Axitinib continuous oral dosing (5 mg twice a day) in the fed state
AG-013736Drug
Axitinib continuous oral dosing (15 mg once a day) in the fed state
AG-013736Drug
Axitinib continuous oral dosing (5 mg twice a day) in the fasted state
AG-013736Drug
Axitinib continuous oral dosing (2 mg twice a day on the first day of dosing, followed by 5 mg twice a day) in the fasted state

Study groups in NCT01469052
Study group	Role	What they receive
Cohort 1	Experimental	Not described Receives: Drug: AG-013736
Cohort 2	Experimental	Not described Receives: Drug: AG-013736
Cohort 3	Experimental	Not described Receives: Drug: AG-013736
Cohort 4	Experimental	Not described Receives: Drug: AG-013736
Cohort 5	Experimental	Not described Receives: Drug: AG-013736
Cohort 6	Experimental	Not described Receives: Drug: AG-013736

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose (MTD)
MTD is defined as the dose level at which "no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD)." DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
Measured: Baseline up to Day 28

Secondary outcomes (10)

Maximum Observed Plasma Concentration (Cmax)
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12).
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2002Aug 2004

First posted10 Nov 2011 (estimated)
Study startNov 2002
Primary completionJul 2004
Study completionAug 2004

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 Solid TumorsStudies 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01469052
Sponsor's protocol ID: AG013736-001
Other IDs: A4060010
Status last verified: Feb 2012
First submitted: 2 Nov 2011
Last updated: 26 Mar 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I, Open-Label, Multicenter, Dose-Escalation Study Of The Tyrosine Kinase Inhibitor Of VEGFR-2, AG013736, In Patients With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT01469052
Acronym / sponsor ID: AG013736-001
Conditions: Advanced Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Nov 2002
Primary completion: Jul 2004 (actual)
Study completion: Aug 2004 (actual)
First posted: 10 Nov 2011 (estimated)
Results: Posted 26 Mar 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of the study was to characterize the safety of investigational agent AG-013736, in patients with solid tumors in this First In Human trial.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Cohort 1	Experimental	Drug: AG-013736
Cohort 2	Experimental	Drug: AG-013736
Cohort 3	Experimental	Drug: AG-013736
Cohort 4	Experimental	Drug: AG-013736
Cohort 5	Experimental	Drug: AG-013736
Cohort 6	Experimental	Drug: AG-013736

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Patients with cytologically or histologically confirmed solid tumor(s) and with at least one measurable disease site
Patients with adequate bone marrow, liver and kidney function
Patients with life expectancy of at least 12 weeks

Key exclusion criteria (2 listed)

Patients who have received chemotherapy, immunotherapy, radiotherapy or any investigational agent within 4 weeks of study entry
Patients with have had a major surgical procedure within 4 weeks of study entry

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
AG-013736Axitinib continuous oral dosing (10 mg once a day, 10 mg twice a day, 20 mg twice a day or 30 mg twice day) in the fed state	Drug	Cohort 1
AG-013736Axitinib continuous oral dosing (20 mg twice a day) in the fed state	Drug	Cohort 2
AG-013736Axitinib continuous oral dosing (5 mg twice a day) in the fed state	Drug	Cohort 3
AG-013736Axitinib continuous oral dosing (15 mg once a day) in the fed state	Drug	Cohort 4
AG-013736Axitinib continuous oral dosing (5 mg twice a day) in the fasted state	Drug	Cohort 5
AG-013736Axitinib continuous oral dosing (2 mg twice a day on the first day of dosing, followed by 5 mg twice a day) in the fasted state	Drug	Cohort 6

Primary outcome

Maximum Tolerated Dose (MTD)
Time frame: Baseline up to Day 28
MTD is defined as the dose level at which "no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD)." DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.

10 secondary outcomes

Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Apparent Oral Clearance (CL/F)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Plasma Decay Half-Life (t1/2)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)

Results and safety

Results posted to the registry on 26 Mar 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed	6	0
Cohort 2: Axitinib 20 mg BID, Fed	4	0
Cohort 3: Axitinib 5 mg BID, Fed	6	0
Cohort 4: Axitinib 15 mg QD, Fed	6	1
Cohort 5: Axitinib 5 mg BID, Fasted	8	0
Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted	6	0

Primary outcome: Maximum Tolerated Dose (MTD)

Time frame: Baseline up to Day 28. Number. Unit: mg BID

Measure	All Treated Participants n = 36
Value	5

Population analysed: Analysis population included all enrolled participants who received at least one dose of the study drug.

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Treated Participants	12 of 36 (33.3%)	36 of 36 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2012.
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.

Related trials for Advanced Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

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

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 AG-013736 in people with Advanced Solid Tumors, run by Pfizer at 3 sites in United States.

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 3 inclusion and 2 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 26 Mar 2012. 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 States. 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 26 Mar 2012). 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?

Maximum Tolerated Dose (MTD) (time frame: Baseline up to Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01469052.

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 26 Mar 2012.