Phase 1
N=116
A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors
Advanced Solid Tumors · Advanced Recurrent Ovarian Tumors
Bottom Line
View on ClinicalTrials.gov: NCT01248949 ↗Enrolled (actual)
116
Serious AEs
44.0%
Results posted
Mar 2017
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicities (DLTs) — 1; 1; 2; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MEDI3617 (Drug); Bevacizumab (Drug); Paclitaxel (Drug); Carboplatin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MedImmune LLC
- Primary completion
- Jul 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
1; 1; 2; 1; 1 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
NA; NA; NA; NA; NA | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
42; 16; 38; 13; 7; 18 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs) |
5; 1; 1; 3; 2; 0 | — |
| PRIMARY Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs) |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs) |
0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs) |
0; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline |
11; 6; 7; 1; 1 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of MEDI3617 |
1.39; NA; NA; NA; NA; 2.44 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617 |
1.3; NA; NA; NA; NA; 2.2 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617 |
1.79; NA; NA; NA; NA; 8.12 | — |
| SECONDARY Systemic Clearance (CL) of MEDI3617 |
2790; NA; NA; NA; NA; 2460 | — |
| SECONDARY Terminal Elimination Half Life (t1/2) of MEDI3617 |
0.585; NA; NA; NA; NA; 1.26 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibody (ADA) |
0; 0; 0; 0; 0 | — |
| SECONDARY Objective Response Rate (ORR) |
1; 1; 2; 2; 0 | — |
| SECONDARY Time to Response (TTR) |
2.6; 1.2; 2.0; 1.7; NA | — |
| SECONDARY Duration of Response (DOR) |
3.7; NA; NA; NA; NA | — |
| SECONDARY Time to Progression (TTP) |
1.4; 11.4; 1.8; 3.5; NA | — |
| SECONDARY Progression-Free Survival (PFS) |
1.4; 11.4; 1.7; 3.5; NA | — |
| SECONDARY Overall Survival (OS) |
11.4; 25.7; 7.4; 14.2; NA | — |
| SECONDARY Circulating Levels of Angiopoietin 2 (Ang2) |
4.07; NA; NA; NA; NA; 4.28 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT01248949). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.