CancerPhase 1MEDI-575NCT00816400
A Dose Escalation, Dose Expansion Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, in Subjects With Advanced Tumors.
A Phase 1 study testing MEDI-575 in people with Cancer, run by MedImmune LLC at 5 sites in United States.
Trial summary
Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- MEDI-575
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 5 sitesUnited States
- Study dates
- 2 Mar 2009to 19 Jan 2012
- 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 confirmed advanced solid tumor for which no curative or standard therapies exist
- Karnofsky performance status of ≥ 60
- Life expectancy of >12 weeks
- Adequate hematologic and organ function
- Negative serum pregnancy test (women only)
- Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential
Who cannot join
- Prior chemotherapy or investigational treatment within 4 weeks of study drug administration
- Prior biological or immunological treatment within 6 weeks of study drug administration
- Concurrent therapy for of cancer
- Major surgery within four weeks or minor surgery within two weeks of study drug administration
- History of diabetes or current treatment for diabetes
- New York Heart Association ≥ Grade 2 congestive heart failure
Show all 12Show fewer
- History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry
- History of other invasive malignancy within 5 years (exceptions are cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that are surgically cured)
- Significant active infection
- Known brain metastases
- Pregnancy or lactation or plans to become pregnant while on study
- Clinically significant abnormality on ECG
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Site
Dallas, Texas
Research Site
Denver, Colorado
Research Site
Indianapolis, Indiana
Research Site
Las Vegas, Nevada
Research Site
Norfolk, Virginia
About this study
Official title: A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, a Fully Human Monoclonal Antibody Directed Against Platelet-derived Growth Factor Receptor Alpha (PDGFRα), in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
- Conditions
- Cancer
- Being tested
- MEDI-575
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI-575Drug
MEDI-575 as an IV infusion
| Study group | Role | What they receive |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Experimental | Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Experimental | MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Experimental | MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Experimental | MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Experimental | MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Experimental | MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Experimental | MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Experimental | MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Experimental | MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. Receives: Drug: MEDI-575 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Number of Participants With Serious Adverse Events
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Laboratory Parameters
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Vital Sign Parameters
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Maximum Tolerated Dose (MTD)
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
Measured: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Secondary outcomes (13)
Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
The concentration of MEDI-575 quantitatively determined in serum samples using a validated electrochemiluminescence (ECL) PK assay. The Cmax after the first dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
The time to reach maximum serum concentration after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
The Cmax/dose after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
The Ctrough ie, measured concentration at the end of a dosing interval (taken directly before next dose administration) of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)
The AUCτ was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose)
The AUCτ/dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
Measured: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
Blood samples for immunogenicity assessments were collected from participants prior to the initiation of infusion of each treatment cycle of MEDI-575. Anti-MEDI-575 antibodies were analyzed using the electro-chemiluminescence (ECL) based method. Only the number of participants positive for anti-MEDI-575 antibodies at any visit are presented.
Measured: Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Percentage of Participants With Objective Response
Objective response rate is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after the initial documentation of response. The CR is defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: From study entry through the end of the study, up to 34 months
Time to Response
Time to response was measured from the start of treatment with MEDI-575 to the first documentation of objective response (confirmed CR or PR). The time to response is assessed only for the participants who have achieved the objective response.
Duration of Response
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was calculated for the subgroup of participants with an objective response.
Time to Progression
Time to progression (TTP) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. TTP was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Measured: Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Progression-free Survival
Progression-free survival (PFS) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause, whichever occurred first. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. PFS was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Measured: Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Overall Survival
Overall survival (OS) is defined as the time from the start of treatment with MEDI-575 until death. For the participants who were alive at the end of study or lost to follow-up, OS was censored on the last date when participants were known to be alive.
Measured: From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2009 (estimated)
- Study start2 Mar 2009
- Primary completion19 Jan 2012
- Study completion19 Jan 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00816400
- Sponsor's protocol ID
- MI-CP187
- Acronym
- MEDI-575
- Status last verified
- Apr 2018
- First submitted
- 23 Dec 2008
- Last updated
- 26 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Becerra CR, Conkling P, Vogelzang N, Wu H, Hong S, Narwal R, Liang M, Tavakkoli F, Pandya N. A phase I dose-escalation study of MEDI-575, a PDGFRalpha monoclonal antibody, in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Nov;74(5):917-25. doi: 10.1007/s00280-014-2567-9. Epub 2014 Aug 23.
PubMed 25149088
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, a Fully Human Monoclonal Antibody Directed Against Platelet-derived Growth Factor Receptor Alpha (PDGFRα), in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
- ClinicalTrials.gov ID
- NCT00816400
- Acronym / sponsor ID
- MEDI-575 / MI-CP187
- Conditions
- Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2009 (actual)
- Primary completion
- 19 Jan 2012 (actual)
- Study completion
- 19 Jan 2012 (actual)
- First posted
- 1 Jan 2009 (estimated)
- Results
- Posted 11 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1) | Experimental | Drug: MEDI-575Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2) | Experimental | Drug: MEDI-575MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3) | Experimental | Drug: MEDI-575MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4) | Experimental | Drug: MEDI-575MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5) | Experimental | Drug: MEDI-575MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6) | Experimental | Drug: MEDI-575MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7) | Experimental | Drug: MEDI-575MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 9.0 mg/kg QWk Expansion Phase | Experimental | Drug: MEDI-575MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
| MEDI-575, 25 mg/kg Q3Wk Expansion Phase | Experimental | Drug: MEDI-575MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed advanced solid tumor for which no curative or standard therapies exist
- Karnofsky performance status of ≥ 60
- Life expectancy of >12 weeks
- Adequate hematologic and organ function
- Negative serum pregnancy test (women only)
Key exclusion criteria (12 listed)
- Prior chemotherapy or investigational treatment within 4 weeks of study drug administration
- Prior biological or immunological treatment within 6 weeks of study drug administration
- Concurrent therapy for of cancer
- Major surgery within four weeks or minor surgery within two weeks of study drug administration
- History of diabetes or current treatment for diabetes
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 |
|---|---|---|
| MEDI-575MEDI-575 as an IV infusion | Drug | MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4), MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5), MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6), MEDI-575, 25 mg/kg Q3Wk Expansion Phase, MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1), MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7), MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2), MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3), MEDI-575, 9.0 mg/kg QWk Expansion Phase |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
Number of Participants With Serious Adverse Events
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
Treatment-emergent Adverse Events Related to Laboratory Parameters
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
Treatment-emergent Adverse Events Related to Vital Sign Parameters
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
Maximum Tolerated Dose (MTD)
Time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
13 secondary outcomes
Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose)
Time frame: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
Time frame: Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Percentage of Participants With Objective Response
Time frame: From study entry through the end of the study, up to 34 months
Time to Response
Duration of Response
Time to Progression
Time frame: Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Progression-free Survival
Time frame: Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Overall Survival
Time frame: From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25149088Becerra CR, Conkling P, Vogelzang N, Wu H, Hong S, Narwal R, Liang M, Tavakkoli F, Pandya N. A phase I dose-escalation study of MEDI-575, a PDGFRalpha monoclonal antibody, in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Nov;74(5):917-25. doi: 10.1007/s00280-014-2567-9. Epub 2014 Aug 23.
- MEDI-575\_CP-187\_Protocol\_Redacted\_28Aug14Link provided by the sponsor.
- PMCID: PMC3749129: Circulating Tumor Cells: Application as a Biomarker for Molecular Characterization and Predictor of Survival in an All-Comer Solid Tumor Phase I Clinical StudyLink 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.
The record lists no contact. Use the official record to reach the sponsor.
5 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 MEDI-575 in people with Cancer, run by MedImmune LLC at 5 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 6 inclusion and 12 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 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 11 Apr 2017). 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 Adverse Events (time frame: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks). The study lists 6 primary outcomes in all. 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 NCT00816400, which also lists 1 linked publication.
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 Jun 2018.