CancerPhase 1NCT01352884
Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer
A Phase 1 study testing AMP-224 in people with Cancer, run by MedImmune LLC at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- AMP-224
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2011to Jan 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
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.
- Conditions
- Cancer
- Being tested
- AMP-224
- Keywords
- Cancer, Carcinoma, Tumor, Solid tumor, Metastatic, Melanoma
- Medical subject headings
- Neoplasms, Carcinoma, Neoplasm Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMP-224Drug
Escalating doses of AMP-224
AMP-224Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 | Experimental | 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. Receives: Drug: AMP-224 |
| Stage 2 | Experimental | 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. Receives: Drug: AMP-224 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From start of study drug administration until withdrawal; through Day 56 of final cycle.
Secondary outcomes (6)
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Screening through 12 weeks post-final cycle.
Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry.
Measured: 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.
Measured: Screening through 12 weeks post-final cycle.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2011 (estimated)
- Study startMar 2011
- Primary completionNov 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01352884
- Sponsor's protocol ID
- AMP-224-01
- Status last verified
- Aug 2016
- First submitted
- 6 May 2011
- Last updated
- 5 Sep 2016
- Results posted
- No
Publications
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.
PubMed 26189934
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01352884
- Acronym / sponsor ID
- AMP-224-01
- Conditions
- Cancer
- Keywords
- Cancer, Carcinoma, Tumor, Solid tumor, Metastatic, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- Mar 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 12 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage 1 | Experimental | Drug: AMP-224Stage 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. |
| Stage 2 | Experimental | Drug: AMP-224Stage 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMP-224Escalating doses of AMP-224 | Drug | Stage 1 |
| AMP-224Stage 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 | Drug | Stage 2 |
Primary outcome
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.
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.
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.
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.
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.
6 secondary outcomes
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.
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.
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2016.
- Derived from this study: PubMed 26189934Borch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMP-224 in people with Cancer, run by MedImmune LLC at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01352884, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2016.