Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer

September 2, 2016 updated by: MedImmune LLC
This is a Phase 1, open-label, multi-center, first time in human study of AMP-224 in adult patients with cancer that is not responding to standard therapy. This study will be conducted in two stages consisting of a Dose-Escalation stage and an Expansion Stage.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Carolina BioOncology Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must be able to provide informed consent
  • In Dose-Escalation: Must have solid tumor malignancy or cutaneous T-cell lymphoma that has relapsed and is refractory to standard therapy, or for which no standard therapy exists
  • In Expansion Phase: Must have melanoma or ovarian cancer that is histologically or cytologically confirmed
  • Ovarian cancer patients must have recurrent of persistent non-mucinous disease, and must not have received more than 2 prior chemotherapeutic regimens
  • Melanoma patients must have recurrent or persistent non-ocular AJCC Stage IIIC or IV disease that is surgically incurable and unresectable
  • Melanoma patients with documented BRAF mutation that is known to be responsive to BRAF inhibitors must have failed or be intolerant to such inhibitors
  • Must have measurable disease
  • Must be able to provide access to archival (Dose-Escalation Phase) and/or fresh tumor tissue (Dose-Escalation and Expansion Phases) at Screening prior to study entry
  • Must by at least 18 years old
  • Must have adequate organ function

Exclusion Criteria:

  • Prior cancer therapies must have completed at least 14 days or 5 half-lives (whichever is longer) prior to first dose of AMP-224
  • Prior treatment with an anti-PD1 antibody therapy
  • Known antibody response against prior antibody therapy or fusion protein therapeutics
  • Major surgery within 4 weeks prior to first dose of AMP-224
  • Prior allogeneic or autologous bone marrow or organ transplantation
  • Known and/or a history or evidence of autoimmune disease except vitiligo, resolved childhood asthma and stable hypothyroidism
  • Received an immunomodulatory drug within 2 weeks of first dose of AMP-224
  • Active infections requiring antibiotics, physician monitoring, or recurrent fevers >100.4 degrees fahrenheit associated with a clinical diagnosis of active infection
  • Patients with cirrhosis
  • Clinically significant cardiac or electrocardiogram abnormalities
  • History or evidence of HIV
  • Active viral disease (except when the viral infection is associated with the malignancy)
  • Regular use of illicit drugs or a recent history of substance abuse
  • Pregnant or breastfeeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Stage 1
Stage 1 will identify the recommended Stage 2 dose using a dose-escalation process. Dose-escalation will continue until either a maximum tolerated dose is established, or a therapeutic dose is reached.
Drug: AMP-224
Escalating doses of AMP-224
Drug: AMP-224
Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood
EXPERIMENTAL: Stage 2
Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood specimens will be evaluated for pharmacodynamic markers/activity at specified timepoints throughout the study.
Drug: AMP-224
Escalating doses of AMP-224
Drug: AMP-224
Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse events.
Time Frame: From start of study drug administration until the date of first documented progression or date of death from any cause; through Day 56 of final cycle.
From start of study drug administration until the date of first documented progression or date of death from any cause; through Day 56 of final cycle.
Number of participants with dose-limiting toxicities.
Time Frame: From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
Number of participants with changes in laboratory values, vital signs, physical exam, and electrocardiogram.
Time Frame: From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities.
Time Frame: From start of study drug administration through Day 28 of Cycle 1.
From start of study drug administration through Day 28 of Cycle 1.
Determine Recommended Phase 2 Dose following analysis of adverse events, pharmacokinetics and changes in laboratory evaluations.
Time Frame: From start of study drug administration until withdrawal; through Day 56 of final cycle.
From start of study drug administration until withdrawal; through Day 56 of final cycle.

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluate pharmacokinetics, including area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax) and clearance of AMP-224 following single and repeat doses of AMP-224.
Time Frame: From Day 0 pre-dose through Day 56 of final cycle.
From Day 0 pre-dose through Day 56 of final cycle.
Evaluate Overall Response Rate (ORR), including Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression-Free Survival (PFS).
Time Frame: From Screening through 12 weeks following final cycle.
From Screening through 12 weeks following final cycle.
Characterization of the effects of AMP-224 on its receptor, PD-1, in peripheral T cells via flow cytometry and correlate with response to treatment.
Time Frame: From Screening until 12 weeks post-final cycle.
From Screening until 12 weeks post-final cycle.
Evaluation and correlation between response to treatment and expression of PD-1 on tumor infiltrating T cells or in available malignant pleural effusions via flow cytometry and/or immunohistochemistry.
Time Frame: Screening through 12 weeks post-final cycle.
Screening through 12 weeks post-final cycle.
Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry.
Time Frame: Screening through 12 weeks post-final cycle.
Screening through 12 weeks post-final cycle.
Identification of peripheral patient selection and pharmacodynamic markers from blood samples that predict and/or correlate with response to treatment.
Time Frame: Screening through 12 weeks post-final cycle.
Screening through 12 weeks post-final cycle.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedImmune LLC

Collaborators

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (ACTUAL)

November 1, 2013

Study Completion (ACTUAL)

January 1, 2014

Study Registration Dates

First Submitted

May 6, 2011

First Submitted That Met QC Criteria

May 11, 2011

First Posted (ESTIMATE)

May 12, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

September 5, 2016

Last Update Submitted That Met QC Criteria

September 2, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • AMP-224-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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