Advanced Solid TumorsPhase 1NCT01248949
A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors
A Phase 1 study testing MEDI3617, Bevacizumab and Paclitaxel in people with Advanced Solid Tumors and Advanced Recurrent Ovarian Tumors, run by MedImmune LLC at 10 sites in United States.
Trial summary
To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced Solid Tumors, Advanced Recurrent Ovarian Tumors
- What is being tested?
- MEDI3617, Bevacizumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 10 sitesUnited States
- Study dates
- Oct 2010to Oct 2015
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
- Patients must be 18 years of age or older
- Karnofsky Performance Status ≥ 70
- Toxicities from previous cancer therapies must have recovered to CTCAE Grade = or < 2
- Adequate organ and marrow function
- Using adequate contraceptive measures, be surgically sterile or post-menopausal
Who cannot join
- Concurrently enrolled in another clinical study, except for non-interventiona observational studies, or if in a follow up period from a previous study
- Receipt of any investigational anticancer therapy within 30 days prior to the first dose of MEDI3617, or in the case of monoclonal antibodies (eg, bevacizumab), 42 days prior to the first dose of MEDI3617
- Current or previous treatment with angiopoietin inhibitors, or inhibitors of Tie1 or Tie2 including, but not limited to, AMG386, CVX-060, XL880, and XL820
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
- Use of immunosuppressive medication or systemic steroids within 7 days prior to first dose of MEDI3617
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Show all 9Show fewer
- Known bleeding diathesis
- Pulmonary hemorrhage or gross hemoptysis within 6 months prior to enrollment
- Therapeutic or palliative radiation therapy within 2 weeks prior to enrollment
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Research Site
Baltimore, Maryland
Research Site
Boston, Massachusetts
Research Site
Buffalo, New York
Research Site
Detroit, Michigan
Research Site
Lafayette, Indiana
Research Site
Los Angeles, California
Research Site
Nashville, Tennessee
Research Site
New York, New York
Research Site
Philadelphia, Pennsylvania
Research Site
Stanford, California
About this study
Official title: Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors
To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.
- Being tested
- MEDI3617, Bevacizumab, Paclitaxel, Carboplatin
- Keywords
- Advanced solid tumors, Advanced recurrent ovarian tumors, MEDI3617, Ang2, Ovarian cancer, Malignant glioma
- Medical subject headings
- Ovarian Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI3617Drug
Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
BevacizumabDrug
Participants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.
PaclitaxelDrug
Participants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons.
CarboplatinDrug
Participants will receive carboplatin via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons.
| Study group | Role | What they receive |
|---|---|---|
| MEDI3617 SINGLE AGENT TOTAL | Experimental | Participants will receive MEDI3617 via intravenous (IV) infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. Receives: Drug: MEDI3617 |
| MEDI3617 + BEVACIZUMAB Q3W ESCALATION | Experimental | Participants will receive MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. Receives: Drug: MEDI3617; Drug: Bevacizumab |
| MEDI3617 + BEVACIZUMAB Q2W TOTAL | Experimental | Participants will receive MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. Receives: Drug: MEDI3617; Drug: Bevacizumab |
| MEDI3617 + PACLITAXEL TOTAL | Experimental | Participants will receive MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. Receives: Drug: MEDI3617; Drug: Paclitaxel |
| MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | Experimental | Participants will receive MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. Receives: Drug: MEDI3617; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
Measured: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
Maximum Tolerated Dose (MTD)
The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
Measured: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product.
Measured: From start of study drug administration up to 90 days after the last dose of MEDI3617
Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)
Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported.
Measured: From start of study drug administration up to 90 days after the last dose of MEDI3617
Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)
Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported.
Measured: From start of study drug administration up to 90 days after the last dose of MEDI3617
Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group.
Measured: From start of study drug administration up to 90 days after the last dose of MEDI3617
Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group.
Measured: From start of study drug administration up to 90 days after the last dose of MEDI3617
Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline
KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead.
Measured: From start of study drug administration up to 30 days after the last dose of MEDI3617
Secondary outcomes (13)
Maximum Observed Serum Concentration (Cmax) of MEDI3617
Cmax is the maximum observed serum concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
Measured: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617
AUC0-last is the Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
Measured: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617
The AUC0-inf is the Area Under the Concentration-Time Curve From Time Zero to infinity of MEDI3617. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
Measured: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Systemic Clearance (CL) of MEDI3617
Systemic clearance describes the removal of drug from a volume of serum in a given unit of time (drug loss from the body). It is measured as milliliter per day (mL/day). Here, "n" is number of participants analyzed for this endpoint at a specific dose.
Measured: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Terminal Elimination Half Life (t1/2) of MEDI3617
The t1/2 is the time in days required for the concentration of the drug to reach half of its original value. Here, "n" is number of participants analyzed for this endpoint at a specific dose.
Measured: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Number of Participants With Positive Anti-Drug Antibody (ADA)
The immunogenic potential of MEDI3617 was assessed by summarizing the number and percentage of participants who develop detectable ADA. Immunogenicity assessment included determination of anti-drug (MEDI3617) antibodies in serum samples. Samples were measured for the presence of ADA using validated immunoassays.
Measured: Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617
Objective Response Rate (ORR)
Objective response rate defined as the number of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Time from the first dose of investigational product until end of study
Time to Response (TTR)
Time to response (TTR) is defined as the time from the study entry to the first documentation of confirmed CR or confirmed PR. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be "0" if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the TTR taken as the first time the response was observed, not the confirmation assessment. TTR was evaluated using the Kaplan-Meier method.
Measured: Time from the first dose of investigational product until end of study
Duration of Response (DOR)
Duration of response is defined as the duration from the first documentation of objective disease response (ie, confirmed CR or confirmed PR) to the first documented disease progression. 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 evaluated for the subgroup of participants with an objective response using the Kaplan-Meier method.
Measured: Time from the first dose of investigational product until end of study
Time to Progression (TTP)
Time to progression (TTP) is defined as time from the start of treatment with MEDI3617 until the documentation of disease progression. 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. Participants having no tumor assessments after the start of treatment with MEDI3617 had TTP censored on the first date of treatment with MEDI3617. TTP was evaluated using the Kaplan-Meier method.
Measured: Time from the first dose of investigational product until end of study
Progression-Free Survival (PFS)
PFS was measured from the start of treatment with MEDI3617 until the documentation of disease progression or death due to any cause, whichever occurred first. 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. Participants having no tumor assessments after the start of treatment with MEDI3617 had PFS censored on the first date of treatment with MEDI3617. PFS was evaluated using the Kaplan-Meier method.
Measured: Time from the first dose of investigational product until end of study
Overall Survival (OS)
Overall survival is defined as the time from the start of treatment with MEDI3617 until death. For the participants who were alive at the end of study or lost to follow-up, overall survival was censored on the last date when participants were known to be alive. Overall survival was evaluated using the Kaplan-Meier method.
Measured: Time from the first dose of investigational product until death due to any cause
Circulating Levels of Angiopoietin 2 (Ang2)
Profile of Ang2 post MEDI3617 administration in relation to time course of antibody concentrations.
Measured: Prior to infusion on Cycle 4 and Cycle 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionJul 2015
- Study completionOct 2015
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.
- 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
- 162 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune, LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01248949
- Sponsor's protocol ID
- CD-ON-MEDI3617-1043
- Status last verified
- Feb 2017
- First submitted
- 23 Nov 2010
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01248949
- Acronym / sponsor ID
- CD-ON-MEDI3617-1043
- Keywords
- Advanced solid tumors, Advanced recurrent ovarian tumors, MEDI3617, Ang2, Ovarian cancer, Malignant glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 162 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Jul 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 25 Nov 2010 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the maximum tolerated dose or optimal biological dose, and the safety profile of MEDI3617 when given as a single-agent or in combination with other chemotherapeutic agents in subjects with advanced solid malignancies resistant to standard therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| MEDI3617 SINGLE AGENT TOTAL | Experimental | Drug: MEDI3617Participants will receive MEDI3617 via intravenous (IV) infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. |
| MEDI3617 + BEVACIZUMAB Q3W ESCALATION | Experimental | Drug: MEDI3617, Drug: BevacizumabParticipants will receive MEDI3617 with bevacizumab via IV infusion every 3 weeks (Q3W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 21 days. |
| MEDI3617 + BEVACIZUMAB Q2W TOTAL | Experimental | Drug: MEDI3617, Drug: BevacizumabParticipants will receive MEDI3617 with bevacizumab via IV infusion every 2 weeks (Q2W) in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. Each cycle consists of 28 days. |
| MEDI3617 + PACLITAXEL TOTAL | Experimental | Drug: MEDI3617, Drug: PaclitaxelParticipants will receive MEDI3617 on Days 1 and 15 with paclitaxel on Days 1, 8, and 15 via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. Each cycle consists of 28 days. |
| MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL | Experimental | Drug: MEDI3617, Drug: Paclitaxel, Drug: CarboplatinParticipants will receive MEDI3617 with carboplatin and paclitaxel on Day 1 via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. Each cycle consists of 21 days. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
- Patients must be 18 years of age or older
- Karnofsky Performance Status ≥ 70
- Toxicities from previous cancer therapies must have recovered to CTCAE Grade = or < 2
- Adequate organ and marrow function
Key exclusion criteria (9 listed)
- Concurrently enrolled in another clinical study, except for non-interventiona observational studies, or if in a follow up period from a previous study
- Receipt of any investigational anticancer therapy within 30 days prior to the first dose of MEDI3617, or in the case of monoclonal antibodies (eg, bevacizumab), 42 days prior to the first dose of MEDI3617
- Current or previous treatment with angiopoietin inhibitors, or inhibitors of Tie1 or Tie2 including, but not limited to, AMG386, CVX-060, XL880, and XL820
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
- Use of immunosuppressive medication or systemic steroids within 7 days prior to first dose of MEDI3617
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 |
|---|---|---|
| MEDI3617Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. | Drug | MEDI3617 + BEVACIZUMAB Q2W TOTAL, MEDI3617 + BEVACIZUMAB Q3W ESCALATION, MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL, MEDI3617 + PACLITAXEL TOTAL, MEDI3617 SINGLE AGENT TOTAL |
| BevacizumabParticipants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons. | Drug | MEDI3617 + BEVACIZUMAB Q2W TOTAL, MEDI3617 + BEVACIZUMAB Q3W ESCALATION |
| PaclitaxelParticipants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons. | Drug | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL, MEDI3617 + PACLITAXEL TOTAL |
| CarboplatinParticipants will receive carboplatin via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons. | Drug | MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
Maximum Tolerated Dose (MTD)
Time frame: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)
The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From start of study drug administration up to 90 days after the last dose of MEDI3617
An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product.
Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)
Time frame: From start of study drug administration up to 90 days after the last dose of MEDI3617
Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported.
Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)
Time frame: From start of study drug administration up to 90 days after the last dose of MEDI3617
Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported.
Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)
Time frame: From start of study drug administration up to 90 days after the last dose of MEDI3617
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group.
Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)
Time frame: From start of study drug administration up to 90 days after the last dose of MEDI3617
An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group.
Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline
Time frame: From start of study drug administration up to 30 days after the last dose of MEDI3617
KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead.
13 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of MEDI3617
Time frame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617
Time frame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617
Time frame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Systemic Clearance (CL) of MEDI3617
Time frame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Terminal Elimination Half Life (t1/2) of MEDI3617
Time frame: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose
Number of Participants With Positive Anti-Drug Antibody (ADA)
Time frame: Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617
Objective Response Rate (ORR)
Time frame: Time from the first dose of investigational product until end of study
Time to Response (TTR)
Time frame: Time from the first dose of investigational product until end of study
Duration of Response (DOR)
Time frame: Time from the first dose of investigational product until end of study
Time to Progression (TTP)
Time frame: Time from the first dose of investigational product until end of study
Progression-Free Survival (PFS)
Time frame: Time from the first dose of investigational product until end of study
Overall Survival (OS)
Time frame: Time from the first dose of investigational product until death due to any cause
Circulating Levels of Angiopoietin 2 (Ang2)
Time frame: Prior to infusion on Cycle 4 and Cycle 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Advanced Solid Tumors
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
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
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant
RecruitingPhase 1
Study of XB010 in Subjects With Solid Tumors
Locally Advanced or Metastatic Solid Tumors, Esophageal Squamous Cell Cancer
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.
MedImmune, LLC study director
MedImmune LLC
10 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 MEDI3617, Bevacizumab and Paclitaxel in people with Advanced Solid Tumors and Advanced Recurrent Ovarian Tumors, run by MedImmune LLC at 10 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 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 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 29 Mar 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 Dose Limiting Toxicities (DLTs) (time frame: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)). The study lists 8 primary outcomes in all. 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 29 Mar 2017.