Clinical trial NCT01352884: Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
Carcinoma
Tumor
Solid tumor
Metastatic
Melanoma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2011-05-12
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Number of participants with adverse events.
timeFrame: 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.
measure: Number of participants with dose-limiting toxicities.
timeFrame: 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.
measure: Number of participants with changes in laboratory values, vital signs, physical exam, and electrocardiogram.
timeFrame: 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.
measure: Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities.
timeFrame: From start of study drug administration through Day 28 of Cycle 1.
measure: Determine Recommended Phase 2 Dose following analysis of adverse events, pharmacokinetics and changes in laboratory evaluations.
timeFrame: From start of study drug administration until withdrawal; through Day 56 of final cycle.
Secondary outcomes:
measure: 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.
timeFrame: From Day 0 pre-dose through Day 56 of final cycle.
measure: Evaluate Overall Response Rate (ORR), including Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression-Free Survival (PFS).
timeFrame: From Screening through 12 weeks following final cycle.
measure: 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.
timeFrame: From Screening until 12 weeks post-final cycle.
measure: 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.
timeFrame: Screening through 12 weeks post-final cycle.
measure: Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry.
timeFrame: Screening through 12 weeks post-final cycle.
measure: Identification of peripheral patient selection and pharmacodynamic markers from blood samples that predict and/or correlate with response to treatment.
timeFrame: Screening through 12 weeks post-final cycle.
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
References:
citation: Borch TH, Donia M, Andersen MH, Svane IM. Reorienting the immune system in the treatment of cancer by using anti-PD-1 and anti-PD-L1 antibodies. Drug Discov Today. 2015 Sep;20(9):1127-34. doi: 10.1016/j.drudis.2015.07.003. Epub 2015 Jul 17.