Advanced CancerPhase 1STMN1-LPNCT01505153
Phase I Intratumoral Pbi-shRNA STMN1 LP in Advanced and/or Metastatic Cancer
A Phase 1 study testing pbi-shRNA STMN1 LP in people with Advanced Cancer and Metastatic Cancer, run by Gradalis, Inc. at 1 site in United States.
Trial summary
This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Metastatic Cancer, Solid Tumors
- What is being tested?
- pbi-shRNA STMN1 LP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to 13 Apr 2017
- 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
- Histologically confirmed advanced and/or metastatic cancer, and, if limited to a single lesion, not considered a candidate for curative surgery or radiation therapy).
- Biopsy accessible lesion.
- Per cohort dose/volume, the volume of the lesion to be injected must be 3x volume of the injectate.
- Subjects that have completed all acceptable therapies with curative potential that are the current standard of care for their respective diseases.
- Recovered from all toxicities (≤ Grade 1) related to prior therapies except for alopecia.
- 1 measurable or evaluable lesion; ≥ 1.8 cm diameter for cohort 1 (see Table 10); injection and biopsy accessible.
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- Age ≥18 years.
- ECOG performance status (PS) 0-2.
- Organ and marrow function as defined below:
- Absolute granulocyte count ≥ 1,500/mm^3 Platelets ≥ 100,000/mm^3 Total bilirubin ≤ 1.5x institutional ULN Creatinine ≤ 2.0 mg/dL
- Ability to understand and the willingness to sign a written informed consent document including permission for pre- and Days 1 and 2 post- injection biopsy and Day 8 injected lesion excision.
- Negative pregnancy test.
Who cannot join
- Surgery involving general anesthesia, chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study.
- Patient must not have received any other investigational agents within 4 weeks prior to study entry.
- Patients with known brain metastases unless treated with whole brain radiation and stable for >/= 2 months or treated with stereotactic radiotherapy only and stable for >/=1 month.
- Short term (<30 days) concurrent systemic steroids ≤0.125 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded.
- Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for >/= 2 years.
- Kaposi's Sarcoma.
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who are pregnant or nursing.
- Patients with known HIV.
- Patients with chronic Hepatitis B and C infection.
- Patients with uncontrolled diseases.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230
About this study
Official title: Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer
This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients with superficially accessible advanced cancer following prior therapies will be entered into the study following a modified dose escalation design based on the demonstrated safety of our previous clinical experience (BB-IND 13744) with the same liposome and vector DNA backbone expressing a different transgene (of which doses up to 7 mg DNA IV/single dose have been administered). Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema (100%-50%-33%-33%) at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose. Should a single, but not more than two (2), ≥ Grade 3 Dose Limiting Toxicity (DLT) occur in any cohort, following mandated review (see below) an additional two (2) patients will be accrued at that dose (total of six). If more than one ≥ Grade 3 toxicity occurs in any cohort, the preceding dose cohort will be expanded to six (from four) and if < 2/6 patients experience ≥ Grade 3 toxicity, that dose will be the Phase II recommended dose. Should no ≥ Grade 3 toxicity occur in any cohort (other than Grade 3 local injection site reaction), an additional two (2) patients will be treated at 0.053 mg/kg DNA intratumoral / single dose.
- Conditions
- Advanced Cancer, Metastatic Cancer, Solid Tumors
- Being tested
- pbi-shRNA STMN1 LP
- Keywords
- Advanced cancer, Metastatic cancer, solid tumors, Melanoma
- Medical subject headings
- Neoplasm Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pbi-shRNA STMN1 LPBiological
This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose.
| Study group | Role | What they receive |
|---|---|---|
| pbi-shRNA STMN1 LP | Experimental | pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Receives: Biological: pbi-shRNA STMN1 LP |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP in patients with superficial advanced and/or metastatic cancer who have no acceptable form of standard therapy.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionMar 2017
- Study completion13 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Advanced 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gradalis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Minal Barve, MD, Principal investigator, Mary Crowley Cancer Research Centers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01505153
- Sponsor's protocol ID
- CL-PTL 103
- Acronym
- STMN1-LP
- Status last verified
- Feb 2018
- First submitted
- 4 Jan 2012
- Last updated
- 22 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Phadke AP, Jay CM, Wang Z, Chen S, Liu S, Haddock C, Kumar P, Pappen BO, Rao DD, Templeton NS, Daniels EQ, Webb C, Monsma D, Scott S, Dylewski D, Frieboes HB, Brunicardi FC, Senzer N, Maples PB, Nemunaitis J, Tong AW. In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human Stathmin 1 oncoprotein. DNA Cell Biol. 2011 Sep;30(9):715-26. doi: 10.1089/dna.2011.1240. Epub 2011 May 25.
PubMed 21612405Rao DD, Maples PB, Senzer N, Kumar P, Wang Z, Pappen BO, Yu Y, Haddock C, Jay C, Phadke AP, Chen S, Kuhn J, Dylewski D, Scott S, Monsma D, Webb C, Tong A, Shanahan D, Nemunaitis J. Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther. 2010 Nov;17(11):780-91. doi: 10.1038/cgt.2010.35. Epub 2010 Jul 2.
PubMed 20596090Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008 Sep;8(9):1461-70. doi: 10.1586/14737140.8.9.1461.
PubMed 18759697
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer
- ClinicalTrials.gov ID
- NCT01505153
- Acronym / sponsor ID
- STMN1-LP / CL-PTL 103
- Conditions
- Advanced Cancer, Metastatic Cancer, Solid Tumors
- Keywords
- Advanced cancer, Metastatic cancer, solid tumors, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Gradalis, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2012 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- 13 Apr 2017 (actual)
- First posted
- 6 Jan 2012 (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 I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients with superficially accessible advanced cancer following prior therapies will be entered into the study following a modified dose escalation design based on the demonstrated safety of our previous clinical experience (BB-IND 13744) with the same liposome and vector DNA backbone expressing a different transgene (of which doses up to 7 mg DNA IV/single dose have been administered). Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema (100%-50%-33%-33%) at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose. Should a single, but not more than two (2), ≥ Grade 3 Dose Limiting Toxicity (DLT) occur in any cohort, following mandated review (see below) an additional two (2) patients will be accrued at that dose (total of six). If more than one ≥ Grade 3 toxicity occurs in any cohort, the preceding dose cohort will be expanded to six (from four) and if < 2/6 patients experience ≥ Grade 3 toxicity, that dose will be the Phase II recommended dose. Should no ≥ Grade 3 toxicity occur in any cohort (other than Grade 3 local injection site reaction), an additional two (2) patients will be treated at 0.053 mg/kg DNA intratumoral / single dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pbi-shRNA STMN1 LP | Experimental | Biological: pbi-shRNA STMN1 LPpbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed advanced and/or metastatic cancer, and, if limited to a single lesion, not considered a candidate for curative surgery or radiation therapy).
- Biopsy accessible lesion.
- Per cohort dose/volume, the volume of the lesion to be injected must be 3x volume of the injectate.
- Subjects that have completed all acceptable therapies with curative potential that are the current standard of care for their respective diseases.
- Recovered from all toxicities (≤ Grade 1) related to prior therapies except for alopecia.
Key exclusion criteria (11 listed)
- Surgery involving general anesthesia, chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study.
- Patient must not have received any other investigational agents within 4 weeks prior to study entry.
- Patients with known brain metastases unless treated with whole brain radiation and stable for >/= 2 months or treated with stereotactic radiotherapy only and stable for >/=1 month.
- Short term (<30 days) concurrent systemic steroids ≤0.125 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded.
- Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for >/= 2 years.
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 |
|---|---|---|
| pbi-shRNA STMN1 LPThis is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose. | Biological | pbi-shRNA STMN1 LP |
Primary outcome
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP
Time frame: 1 month
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP in patients with superficial advanced and/or metastatic cancer who have no acceptable form of standard therapy.
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 22 Feb 2018.
- Background: PubMed 21612405Phadke AP, Jay CM, Wang Z, Chen S, Liu S, Haddock C, Kumar P, Pappen BO, Rao DD, Templeton NS, Daniels EQ, Webb C, Monsma D, Scott S, Dylewski D, Frieboes HB, Brunicardi FC, Senzer N, Maples PB, Nemunaitis J, Tong AW. In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human Stathmin 1 oncoprotein. DNA Cell Biol. 2011 Sep;30(9):715-26. doi: 10.1089/dna.2011.1240. Epub 2011 May 25.
- Background: PubMed 20596090Rao DD, Maples PB, Senzer N, Kumar P, Wang Z, Pappen BO, Yu Y, Haddock C, Jay C, Phadke AP, Chen S, Kuhn J, Dylewski D, Scott S, Monsma D, Webb C, Tong A, Shanahan D, Nemunaitis J. Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther. 2010 Nov;17(11):780-91. doi: 10.1038/cgt.2010.35. Epub 2010 Jul 2.
- Background: PubMed 18759697Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008 Sep;8(9):1461-70. doi: 10.1586/14737140.8.9.1461.
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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.
Minal Barve, MD principal investigator
Mary Crowley Cancer Research Centers
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 pbi-shRNA STMN1 LP in people with Advanced Cancer and Metastatic Cancer, run by Gradalis, Inc. 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 12 inclusion and 11 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 22 Feb 2018. 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?
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP (time frame: 1 month). 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 NCT01505153, which also lists 3 linked publications.
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 22 Feb 2018.