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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01248949
First received: November 23, 2010
Last updated: September 26, 2014
Last verified: September 2014

November 23, 2010
September 26, 2014
October 2010
August 2016   (final data collection date for primary outcome measure)
  • Determine the maximum tolerable dose (MTD) or optimal biological dose (OBD) of MEDI3617 [ Time Frame: Up until 90 days after the last dose of MED3617 ] [ Designated as safety issue: Yes ]
    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
  • Determine the safety of MEDI3617 by evaluating adverse events, serious adverse events, and changes in clinical and laboratory evaluations. [ Time Frame: Up until 90 days after the last dose of MEDI3617 ] [ Designated as safety issue: Yes ]
    Safety will be evaluated using standard safety assessments.
Determine the maximum tolerable dose or optimal biological dose of MEDI3617 in subjects with advanced solid malignances refractory to standard therapy or for which no standard therapy exists [ Time Frame: 21 days - 105 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01248949 on ClinicalTrials.gov Archive Site
  • Pharmacokinetic Assessment [ Time Frame: During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up ] [ Designated as safety issue: No ]
    Determine AUC, Cmax, CL, half-life (t1/2) of MEDI3617
  • Immunogenicity Assessment [ Time Frame: During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up ] [ Designated as safety issue: No ]
    Assess antidrug antibodies
  • Efficacy Assessments [ Time Frame: During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up ] [ Designated as safety issue: No ]
    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
  • Determine circulating levels of Ang1 and Ang2 [ Time Frame: During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up ] [ Designated as safety issue: No ]
    Evaluate the profiles of both circulating levels of Ang2 and Ang1 post MEDI3617 administration
  • Pharmacodynamic assessments [ Time Frame: During treatment phase, end of treatment, 30 days after the last dose, and every 3 months during follow-up ] [ Designated as safety issue: No ]
    Evaluate relationship between MEDI3617 and baseline levels of Ang 2, Tie2, and microvessel density in subjects with advanced recurrent ovarian cancer.
Describe the pharmacokinetics of MEDI3617, determine its immunogenicity, determine the pharmacodynamics of MEDI3617 on circulating levels of Ang2 and Ang1, and evaluate the antitumor activity of MEDI3617 [ Time Frame: 21 days - 105 days ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study to Evaluate the Safety and Antitumor Activity in Subjects With Advanced Solid Tumors
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Solid Tumors
  • Advanced Recurrent Ovarian Tumors
  • 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
  • Drug: MEDI3617 + Bev Q3W Dose Escalation
    1 of 4 doses MEDI3617 + bev at 15mg/kg every 21 days
  • Drug: MEDI3617 + Bev Q2W Dose Escalation
    1 of 4 doses MEDI3617 + bev at 10mg/kg every 28 days
  • Drug: 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.
  • Drug: 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
  • Drug: 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
  • Drug: 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
  • Drug: 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
  • Experimental: MEDI3617-Dose Escalation All SolidTumors
    1 of 7 doses of MEDI3617 (ex: Dose 1, 2, 3, etc) given as IV infusions q 21 days until unacceptable toxicity, documented disease progression, or other reasons. This arm could enroll 24-42 subjects.
    Intervention: Drug: MEDI3617
  • Experimental: MEDI3617 + Bev Q3W Dose Escalation
    1 of 4 doses of MEDI3617 with bevacizumab (15mg/kg) via IV infusion every 21 days until unacceptable toxicity, documented disease progression, or other reasons. This arm could enroll 12-24 subjects.
    Intervention: Drug: MEDI3617 + Bev Q3W Dose Escalation
  • Experimental: MEDI3617 + Bev Q2W Dose Escalation
    1 of 4 doses of MEDI3617 with bevacizumab (10mg/kg) via IV infusion every 28 days until unacceptable toxicity, documented disease progression, or other reasons. This arm could enroll 12-24 subjects.
    Intervention: Drug: MEDI3617 + Bev Q2W Dose Escalation
  • Experimental: Malignant Glioma Dose Expansion
    Up to 2 additional dose-expansion arms will evaluate the activity of MEDI3617 in combination with bevacizumab in subjects with recurrent malignant glioma who are naive to bevacizumab or refractory to bevacizumab based on preliminary activity of the combination MEDI3617 and bevacizumab in subjects with recurrent malignant glioma. Each dose-expansion arm may enroll 15 to 60 subjects. Subjects will receive MEDI3617 in combination with bevacizumab until unacceptable toxicity, documentation of disease progression or other reasons for subject withdrawal. Enrollment of 15-120 subjects.
    Intervention: Drug: Optional Dose Expansion
  • Experimental: MEDI3617 + Weekly Pax Dose Escalation
    Cohorts of 3 to 6 evaluable subjects will each receive 1 of 2 doses of MEDI3617 on Days 1 and 15 and paclitaxel 80 mg/m2 on Days 1, 8, and 15 via IV infusion every 28 days until unacceptable toxicity, documentation of disease progression, or other reasons. Enrollment of 6 to 12 subjects.
    Intervention: Drug: MEDI3617 + Weekly Pax Dose Escalation
  • Experimental: MEDI3617 + Pax & Carbo Q3W Dos Esc
    Cohorts of 3 to 6 evaluable subjects will each receive 1 of 2 doses of MEDI3617 (MTD/OBD-1 or MTD/OBD), carboplatin (AUC 5 by Calvert formula), and paclitaxel (175 mg/m2) on Day 1 via IV infusion every 21 days for up to 6 cycles (cycle length = 21 days) or until unacceptable toxicity, documentation of disease progression, or other reasons. Enrollment of 6-12 subjects.
    Intervention: Drug: MEDI3617 + Pax & Carbo Q3W Dos Esc
  • Experimental: MEDI3617 + Gem & Carbo Q3W Dos Esc
    Cohorts of 3 to 6 evaluable subjects will each receive 1 of 2 doses of MEDI3617 (MTD/OBD-1 or MTD/OBD) on Day 1, gemcitabine (1000 mg/m2) on Days 1 and 8, and carboplatin (AUC 4 by Calvert formula) on Day 1 via IV infusion every 21 days for up to 6 cycles (cycle length = 21 days) or until unacceptable toxicity, documentation of disease progression, or other reasons. Enrollment of 6-12 subjects.
    Intervention: Drug: MEDI3617 + Gem & Carbo Q3W Dos Esc
  • Experimental: Advanced Recurrent Ovarian Tumors
    Upon completion of the single-agent dose-escalation phase, 25 subjects with advanced recurrent ovarian cancer will receive MEDI3617 at the MTD/OBD dose level tested as a single-agent
    Intervention: Drug: Advanced Recurrent Ovarian Tumors
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
August 2016
August 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 ClinicalTrialEnquiries@Medimmune.com
United States
 
NCT01248949
CD-ON-MEDI3617-1043
No
MedImmune LLC
MedImmune LLC
Not Provided
Study Director: Dominic Lai, MD MedImmune LLC
MedImmune LLC
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP