Refractory Solid TumorsPhase 1NCT00914914
Safety Study of a Cell Penetrating Peptide (p28) to Treat Solid Tumors That Resist Standard Methods of Treatment
A Phase 1 study testing p28 in people with Refractory Solid Tumors, run by Dr. Tapas K. Das Gupta at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety of an experimental drug (p28) as a treatment for certain advanced cancers which express a protein called p53 and which have not responded to prior treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Solid Tumors
- What is being tested?
- p28
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Jun 2011
- 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
- Patients must have histologically proven solid tumor disease with documentation of measurable metastatic disease as defined by RECIST.
- The term refractory solid tumor signifies patients with metastatic solid tumors who have failed all standard therapy or for whom no standard therapy exists.
- In patients with refractory solid tumors, a pretreatment biopsy (either of the original primary or metastatic deposit) must show p53 (wild-type and to an extent mutant) expression by means of immunocytochemistry.
- Patients must have distant metastases or unresectable local disease, but a projected life expectancy of at least 6 months.
- Patients must have signed an informed consent.
- This study is confined to adults of both sexes, age 18 or older.
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- Patients must have no medical problems that would pose an undue risk or that would limit full compliance with the study.
- A minimum of 4 weeks must have elapsed since the completion of prior therapy, including hormonal therapy, chemotherapy, radiation therapy, immunotherapy, oral tyrosine kinase inhibitors and monoclonal antibodies.
- Adequate baseline organ function assessed by the following laboratory values within 30 days prior to study entry:
- Granulocyte count >1,500/mm3, hematocrit >30%, and platelets >100,000/mm3.
- Calculated creatinine clearance >50ml/min.
- Adequate liver function with SGOT, SGPT, LDH, and alkaline phosphatase <3 x the upper limit of normal; serum bilirubin <2.0 mg/dl.
- PT and PTT not more than 1.5 times the upper limit of normal.
- Adequate cardiac and pulmonary function. Patients with decreased LVEF or PFTs will be evaluated by a cardiologist or pulmonary physician prior to enrollment of this protocol.
Who cannot join
- Patients who are undergoing chemotherapy or immunotherapy, i.e., cytokines
- Patients with refractory solid tumors whose primary tumor or metastatic deposits do not express p53 (null) will not be eligible.
- Patients with serious additional illness, including HIV, hepatitis, or untreated active infection.
- Patients with any underlying conditions that would contraindicate therapy with the study agent.
- Patients with a history of prior malignancy in the past five years other than the current problem for which he/she is being considered for this trial (patients with prior history of basal cell carcinoma or squamous cell skin cancer are eligible).
- Patients with any other serious medical, i.e., cardiovascular, uncontrolled diabetes (insulin resistant), or psychiatric illness that would prevent informed consent will not be eligible to participate in the study.
- Patients who are either pregnant or lactating (all patients of childbearing potential will receive a pregnancy test within 2 days of study initiation).
- Brain Metastases, current or past (unless treated at least one year prior to enrollment).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago Department of Surgical Oncology
Chicago, Illinois, 60612
About this study
Official title: A Phase I Trial of p28 (Cell Penetrating Peptide) in the Treatment of Refractory Solid Tumors
The purpose of this study is to evaluate the safety of an experimental drug (p28) as a treatment for certain advanced cancers which express a protein called p53 and which have not responded to prior treatment.
Read the detailed description
The drug used in this study is p28, a cancer cell killing peptide. A peptide is a compound made of amino acids, which are substances that the body uses to make protein. The p28 peptide was created from a protein called azurin. Azurin is created by a common disease-causing bacteria named Pseudomonas Aeruginosa. p28 is experimental and has not yet been tested in humans and has not been approved by the FDA for use in cancer subjects.
Up to 30 subjects may be enrolled in order to find 15 subjects who qualify for the study.
Subjects will be enrolled in groups of three, each starting at one of five progressively higher dosage groups. The first group of three subjects will receive the lowest dose of p28 three times a week injected into a vein for four weeks. They will then be monitored for two weeks. If no bad side effects are recorded, the initial three subjects will then receive the second (higher) dose level of p28 three times a week for another four weeks, followed, again, by two weeks of follow up. Additionally, three new subjects will be added to the study and receive p28 on the same schedule, although this second group will start with the second dose level. In this manner, 3 new subjects will be added every six weeks and start treatment at the dose level to which previously enrolled groups have now progressed.
Subjects will be monitored weekly during their first six weeks and then every two weeks for the remainder of the study. Monitoring will include physical exams, blood tests, EKG, and appropriate radiographic imaging (CT, MRI, PET scan, and/or chest X-ray).
The entire study should take 32 weeks for subjects starting at dose 1, 26 weeks for subjects starting at dose 2, 20 weeks for subjects starting at dose 3, 14 weeks for subjects starting at dose 4, and 8 weeks for subjects starting at dose 5 (there is an additional 2 week follow-up period at the end of the study for all subjects included in these figures). All surviving subjects however, will be followed according to the normal follow-up schedule for such subjects at the UIC Oncology Center.
- Conditions
- Refractory Solid Tumors
- Being tested
- p28
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
p28Drug
Also called azurin
p28 will be dissolved in normal saline and infused intravenously into the patient over 15-30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| p28 Phase I Safety | Experimental | A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3þ3 dose escalation design. Receives: Drug: p28 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and laboratory adverse reactions will be closely monitored by periodic physical and laboratory examination.
Measured: 32 weeks
Grade 3 non-hematologic or Grade 4 hematologic toxicity will also define the Maximum Feasible Dose (MFD).
Measured: 32 weeks
Secondary outcomes (2)
Reduction in the size of measurable tumors using the RECIST criteria and, if possible, demonstration of p28 localization and biopsy of tumor.
Measured: 32 weeks
Calculate peak (serum) concentration of p28 and compare with any sign of toxicity and response.
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2009 (estimated)
- Study startApr 2009
- Primary completionApr 2011
- Study completionJun 2011
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 Refractory Solid TumorsStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Tapas K. Das Gupta
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor-investigator, Dr. Tapas K. Das Gupta, CDG Therapeutics, Inc.
- Investigators
- Michael A Warso, M.D., Principal investigator, University of Illinois Department of Surgical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00914914
- Sponsor's protocol ID
- CDGTI-p28-001
- Other IDs
- IND 77754, 2008-0213, PAF 2009-03370
- Status last verified
- Oct 2014
- First submitted
- 3 Jun 2009
- Last updated
- 28 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Warso MA, Richards JM, Mehta D, Christov K, Schaeffer C, Rae Bressler L, Yamada T, Majumdar D, Kennedy SA, Beattie CW, Das Gupta TK. A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours. Br J Cancer. 2013 Mar 19;108(5):1061-70. doi: 10.1038/bjc.2013.74. Epub 2013 Feb 28.
PubMed 23449360
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of p28 (Cell Penetrating Peptide) in the Treatment of Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00914914
- Acronym / sponsor ID
- CDGTI-p28-001
- Conditions
- Refractory Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Dr. Tapas K. Das GuptaIndustry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 5 Jun 2009 (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.
The purpose of this study is to evaluate the safety of an experimental drug (p28) as a treatment for certain advanced cancers which express a protein called p53 and which have not responded to prior treatment.
Detailed description
The drug used in this study is p28, a cancer cell killing peptide. A peptide is a compound made of amino acids, which are substances that the body uses to make protein. The p28 peptide was created from a protein called azurin. Azurin is created by a common disease-causing bacteria named Pseudomonas Aeruginosa. p28 is experimental and has not yet been tested in humans and has not been approved by the FDA for use in cancer subjects.
Up to 30 subjects may be enrolled in order to find 15 subjects who qualify for the study.
Subjects will be enrolled in groups of three, each starting at one of five progressively higher dosage groups. The first group of three subjects will receive the lowest dose of p28 three times a week injected into a vein for four weeks. They will then be monitored for two weeks. If no bad side effects are recorded, the initial three subjects will then receive the second (higher) dose level of p28 three times a week for another four weeks, followed, again, by two weeks of follow up. Additionally, three new subjects will be added to the study and receive p28 on the same schedule, although this second group will start with the second dose level. In this manner, 3 new subjects will be added every six weeks and start treatment at the dose level to which previously enrolled groups have now progressed.
Subjects will be monitored weekly during their first six weeks and then every two weeks for the remainder of the study. Monitoring will include physical exams, blood tests, EKG, and appropriate radiographic imaging (CT, MRI, PET scan, and/or chest X-ray).
The entire study should take 32 weeks for subjects starting at dose 1, 26 weeks for subjects starting at dose 2, 20 weeks for subjects starting at dose 3, 14 weeks for subjects starting at dose 4, and 8 weeks for subjects starting at dose 5 (there is an additional 2 week follow-up period at the end of the study for all subjects included in these figures). All surviving subjects however, will be followed according to the normal follow-up schedule for such subjects at the UIC Oncology Center.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| p28 Phase I Safety | Experimental | Drug: p28A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3þ3 dose escalation design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have histologically proven solid tumor disease with documentation of measurable metastatic disease as defined by RECIST.
- The term refractory solid tumor signifies patients with metastatic solid tumors who have failed all standard therapy or for whom no standard therapy exists.
- In patients with refractory solid tumors, a pretreatment biopsy (either of the original primary or metastatic deposit) must show p53 (wild-type and to an extent mutant) expression by means of immunocytochemistry.
- Patients must have distant metastases or unresectable local disease, but a projected life expectancy of at least 6 months.
- Patients must have signed an informed consent.
Key exclusion criteria (8 listed)
- Patients who are undergoing chemotherapy or immunotherapy, i.e., cytokines
- Patients with refractory solid tumors whose primary tumor or metastatic deposits do not express p53 (null) will not be eligible.
- Patients with serious additional illness, including HIV, hepatitis, or untreated active infection.
- Patients with any underlying conditions that would contraindicate therapy with the study agent.
- Patients with a history of prior malignancy in the past five years other than the current problem for which he/she is being considered for this trial (patients with prior history of basal cell carcinoma or squamous cell skin cancer are eligible).
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 |
|---|---|---|
| p28Also: azurinp28 will be dissolved in normal saline and infused intravenously into the patient over 15-30 minutes. | Drug | p28 Phase I Safety |
Primary outcome
Clinical and laboratory adverse reactions will be closely monitored by periodic physical and laboratory examination.
Time frame: 32 weeks
Grade 3 non-hematologic or Grade 4 hematologic toxicity will also define the Maximum Feasible Dose (MFD).
Time frame: 32 weeks
2 secondary outcomes
Reduction in the size of measurable tumors using the RECIST criteria and, if possible, demonstration of p28 localization and biopsy of tumor.
Time frame: 32 weeks
Calculate peak (serum) concentration of p28 and compare with any sign of toxicity and response.
Time frame: 32 weeks
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 28 Oct 2014.
- Background: PubMed 23449360Warso MA, Richards JM, Mehta D, Christov K, Schaeffer C, Rae Bressler L, Yamada T, Majumdar D, Kennedy SA, Beattie CW, Das Gupta TK. A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours. Br J Cancer. 2013 Mar 19;108(5):1061-70. doi: 10.1038/bjc.2013.74. Epub 2013 Feb 28.
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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.
Michael A Warso, M.D. principal investigator
University of Illinois Department of Surgical Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing p28 in people with Refractory Solid Tumors, run by Dr. Tapas K. Das Gupta at 1 site 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 14 inclusion and 8 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 28 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Clinical and laboratory adverse reactions will be closely monitored by periodic physical and laboratory examination. (time frame: 32 weeks). The study lists 2 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 NCT00914914, 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 28 Oct 2014.