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

Purpose

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.

Condition	Intervention	Phase
Cancer	Drug: AMP-224	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Amplimmune:

Primary Outcome Measures:

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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]

Estimated Enrollment:	63
Study Start Date:	March 2011
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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
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 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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352884

Locations

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

Sponsors and Collaborators

Amplimmune

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Amplimmune
ClinicalTrials.gov Identifier:	NCT01352884 History of Changes
Other Study ID Numbers:	AMP-224-01
Study First Received:	May 6, 2011
Last Updated:	January 24, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amplimmune:

Cancer
Carcinoma
Tumor

Solid tumor
Metastatic
Melanoma

ClinicalTrials.gov processed this record on May 22, 2013