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

NCT01248949 | Completed Phase 1 Results

• 1 other identifier: CD-ON-MEDI3617-1043
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Advanced Solid Tumors; Advanced Recurrent Ovarian Tumors

Keywords

Advanced solid tumors; Advanced recurrent ovarian tumors; MEDI3617; Ang2; Ovarian cancer; Malignant glioma

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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

  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

  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

  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

  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

Study Arms (5)

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.

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.

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.

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.

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.

Drug: MEDI3617; Drug: Paclitaxel; Drug: Carboplatin

Interventions

MEDI3617 DRUG

Participants will receive MEDI3617 via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.

MEDI3617 + BEVACIZUMAB Q2W TOTAL; MEDI3617 + BEVACIZUMAB Q3W ESCALATION; MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL; MEDI3617 + PACLITAXEL TOTAL; MEDI3617 SINGLE AGENT TOTAL

Bevacizumab DRUG

Participants will receive bevacizumab via IV infusion in each cycle until unacceptable toxicity, initiation of alternative anticancer treatment, documented disease progression, or other reasons.

MEDI3617 + BEVACIZUMAB Q2W TOTAL; MEDI3617 + BEVACIZUMAB Q3W ESCALATION

Paclitaxel DRUG

Participants will receive paclitaxel via IV infusion in each cycle until unacceptable toxicity, documented disease progression, or other reasons.

MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL; MEDI3617 + PACLITAXEL TOTAL

Carboplatin DRUG

Participants will receive carboplatin via IV infusion in each cycle until unacceptable toxicity, documentation of disease progression, or other reasons.

MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (10)

Research Site

Los Angeles, California, United States

Location

Research Site

Stanford, California, United States

Location

Research Site

Lafayette, Indiana, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Boston, Massachusetts, United States

Location

Research Site

Detroit, Michigan, United States

Location

Research Site

Buffalo, New York, United States

Location

Research Site

New York, New York, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Glioma

Interventions

MEDI3617; Bevacizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Mohammed Dar, MD
• Organization: MedImmune, LLC

information.center@astrazeneca.com

301-398-0000

Study Officials

• MedImmune, LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2010
• First Posted: November 25, 2010
• Study Start: October 1, 2010
• Primary Completion: July 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

US (10)