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

This study is currently recruiting participants.
Verified December 2013 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01248949
First received: November 23, 2010
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Advanced Recurrent Ovarian Tumors
Drug: MEDI3617
Drug: MEDI3617 + Bev Q3W Dose Escalation
Drug: MEDI3617 + Bev Q2W Dose Escalation
Drug: Optional Dose Expansion
Drug: MEDI3617 + Weekly Pax Dose Escalation
Drug: MEDI3617 + Pax & Carbo Q3W Dos Esc
Drug: MEDI3617 + Gem & Carbo Q3W Dos Esc
Drug: Advanced Recurrent Ovarian Tumors
Phase 1

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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 183
Study Start Date: October 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Drug: MEDI3617 + Bev Q3W Dose Escalation
1 of 4 doses MEDI3617 + bev at 15mg/kg every 21 days
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.
Drug: MEDI3617 + Bev Q2W Dose Escalation
1 of 4 doses MEDI3617 + bev at 10mg/kg every 28 days
Experimental: Optional Dose Expansion
Up to 2 additional dose-expansion arms may be evaluated at the sponsor's discretion with each dose-expansion arm enrolling up to 16 subjects. Selection of the tumor type and MEDI3617 treatment regimen will be based on any previous observed signal of antitumor activity and acceptable safety profile of MEDI3617 in any of the single-agent or combination dose-escalation cohorts. Subjects may receiive MEDI3617 as monotherapy or in combination with bevacizumab or chemotherapy until unacceptable toxicity, documentation of disease progression or other reasons for subject withdrawal. Up to 32 additional subjects may be enrolled into the study.
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.
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.
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
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.
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
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.
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
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
Drug: Advanced Recurrent Ovarian Tumors
25 subjects to receive MEDI3617 at the MTD/OBD dose tested as a single-agent via IV infusion every 21 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01248949

Contacts
Contact: Michele Jordan ClinicalTrialTransparency@astrazeneca.com

Locations
United States, California
Research Site Recruiting
Los Angeles, California, United States, 90048
Research Site Recruiting
Stanford, California, United States, 94305
United States, Indiana
Research Site Recruiting
Lafayette, Indiana, United States, 47905
United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02114
Research Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site Recruiting
Detroit, Michigan, United States, 48201
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14263
Research Site Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Robert Sikorski, MD, PhD MedImmune LLC
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01248949     History of Changes
Other Study ID Numbers: CD-ON-MEDI3617-1043
Study First Received: November 23, 2010
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Advanced solid tumors
Advanced recurrent ovarian tumors
MEDI3617
Ang2

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 16, 2014