A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01248949
• Other study ID #: CD-ON-MEDI3617-1043
• Status: Completed
• Phase: Phase 1
• First received: November 23, 2010
• Last updated: December 3, 2015
• Start date: October 2010
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: October 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Recurrent Ovarian Tumors
• Advanced Solid Tumors
• Neoplasms
• Ovarian Neoplasms

Intervention

Drug:
• MEDI3617
1 of 7 doses of MEDI3617 given (ex: Dose 1, 2, 3, etc) every 21 days in order to determine two safe and tolerated doses that will be used in the dose expansion phase as both Dose Level A and Dose Level B
• MEDI3617 + Bev Q3W Dose Escalation
1 of 4 doses MEDI3617 + bev at 15mg/kg every 21 days
• MEDI3617 + Bev Q2W Dose Escalation
1 of 4 doses MEDI3617 + bev at 10mg/kg every 28 days
• Optional Dose Expansion
Up to 2 additional dose-expansion arms may be evaluated at the sponsor's discretion. MEDI3617 will be administered every 21 or 28 days as a single-agent or in combination with bevacizumab or chemotherapy depending on the dosing regimen that is selected.
• MEDI3617 + Weekly Pax Dose Escalation
IV infusions of MEDI3617 at MTD/OBD-1 or MTD/OBD Q2W (Days 1, 15) + 80 mg/m2 weekly paclitaxel (Days 1, 8, 15) every 28 days
• MEDI3617 + Pax & Carbo Q3W Dos Esc
IV infusions of MEDI3617 at MTD/OBD-1 or MTD/OBD Q3W (Day 1) + AUC5 carboplatin (Day 1) + 175 mg/m2 paclitaxel (Day 1) evey 21 days
• MEDI3617 + Gem & Carbo Q3W Dos Esc
IV infusions of MEDI3617 at MTD/OBD-1 or MTD/OBD Q3W (Day 1) + 1000 mg/m2 gemcitabine (Days 1, 8) + AUC4 carboplatin (Day 1) evey 21 days
• Advanced Recurrent Ovarian Tumors
Up to 25 subjects to receive MEDI3617 at the MTD/OBD dose tested as a single-agent via IV infusion every 21 days

Locations

Country	Name	City	State
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Buffalo	New York
United States	Research Site	Detroit	Michigan
United States	Research Site	Lafayette	Indiana
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the maximum tolerable dose (MTD) or optimal biological dose (OBD) of MEDI3617	Determine the maximum tolerable dose or optimal biological dose of MEDI3617 administered as a single-agent, MEDI3617 co-administered with bevacizumab or weekly paclitaxel monotherapy, or MEDI3617 co-administered with carboplatin plus paclitaxel or carboplatin plus gemcitabine combination chemotherapies in subjects with advanced solid malignances refractory to standard therapy or for which no standard therapy exists	Up until 90 days after the last dose of MED3617	Yes
Primary	Determine the safety of MEDI3617 by evaluating adverse events, serious adverse events, and changes in clinical and laboratory evaluations.	Safety will be evaluated using standard safety assessments.	Up until 90 days after the last dose of MEDI3617	Yes
Secondary	Pharmacokinetic Assessment	Determine AUC, Cmax, CL, half-life (t1/2) of MEDI3617	During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up	No
Secondary	Immunogenicity Assessment	Assess antidrug antibodies	During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up	No
Secondary	Efficacy Assessments	Assess objective response rate (ORR), time to progression (TTP), duration of response (DR), time to response (TTR), progression-free survival (PFS), overall survival (OS) of MEDI3617	During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up	No
Secondary	Determine circulating levels of Ang1 and Ang2	Evaluate the profiles of both circulating levels of Ang2 and Ang1 post MEDI3617 administration	During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up	No
Secondary	Pharmacodynamic assessments	Evaluate relationship between MEDI3617 and baseline levels of Ang 2, Tie2, and microvessel density in subjects with advanced recurrent ovarian cancer.	During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up	No

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