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NeoplasmPhase 1SGT94-01NCT01517464

A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors

A Phase 1 study testing SGT-94 in people with Neoplasm, run by SynerGene Therapeutics, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase I study designed to evaluate the safety and maximum tolerated dose (MTD) of SGT-94, a novel, tumor-targeted, systemic gene therapy agent for cancer. In addition, we will look for evidence of RB94 expression within tumor tissue after systemic administration of SGT-94. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasm
What is being tested?
SGT-94
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Jan 2012to Dec 2015
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

  • Histologic proof of cancer for which no standard therapy is available, and which shows no staining for RB by IHC.
  • Spirometry with at least 70% of predicted volumes (including FEV1). A left ventricular ejection fraction (LVEF) of 45% or more. All patients will have a screening 2-D Echocardiogram as part of eligibility screening.
  • Patients must have adequate physiologic reserve as evidenced by:
  • Zubrod Performance Status (PS) of </= 2; or 3 if of recent onset (i.e. < 2 weeks) and if the compromised performance status is related to uncontrolled pain which is expected to come under control by means of improved pain management.
  • Laboratory values meeting the following criteria:
  • Absolute neutrophil count >/= 1,200/mm3
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  • Platelet count >100,000/mm3.
  • AST and ALT </= 3x the upper limit of normal
  • Conjugated bilirubin </= 1.5 mg/dL (or total bilirubin </= 2.5 mg/dL)
  • Native kidney function producing creatinine clearance (either measured or estimated by Cockcroft formula) of at least 40 mL/min. Cockcroft formula: CLcr = [(140-age) • wt(kg)]/[72 •Creat (mg/dL)] (For females, multiply by 0.85)
  • Hemoglobin >/= 10.0 g/dL without transfusion support
  • White blood cell count > 3.0 k/mm3
  • PT and aPTT each < 1.5 times the upper limit of normal.
  • Women of child-bearing potential must have a negative pregnancy test.
  • Male and female patients reproductive potential must agree to use measures to avoid pregnancy throughout the study and for 3 months following discontinuing study drug.
  • Patients must have recovered from any previous therapy side effects or toxicities prior to initiating protocol study infusions.
  • Life expectancy > 12 weeks.
  • Organ function </= grade 1.
  • Age of </= 18 years.

Who cannot join

  • Some prior cancer therapies are not consistent with eligibility; specifically:
  • At least 30 days must have elapsed since any prior experimental therapy
  • At least 6 weeks must have elapsed since prior systemic mitomycin C
  • At least 8 weeks must have elapsed since any dose of Strontium-89
  • At least 4 weeks must have elapsed since prior Sm-153 lexidronam (Quadramet™)
  • At least 4 weeks must have elapsed since prior radiotherapy
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  • Any prior exposure to gene vector delivery products
  • Pregnancy or lactation
  • Serious concurrent medical illness that in the opinion of the investigator would compromise patient safety or preclude accurate assessment of outcome.
  • Patients with the following manifestations of cardiovascular disease are excluded:
  • Myocardial infarction (MI) within the previous six months, or patients with left ventricular ejection fraction of less than 45% secondary to a more remote MI.
  • Any history of CVA or TIA in previous six months
  • New York Heart Association grade 2 or greater congestive failure
  • Unstable angina defined as angina (or anginal equivalent) 2 or more times per week despite medical therapy.
  • Echocardiographic evidence of pulmonary hypertension.
  • Diastolic dysfunction felt to contribute to any clinical sign or symptom.
  • Uncontrolled hypertension, defined as systolic BP >140 or diastolic >90 despite therapy.
  • Serious concurrent psychiatric disorder that in the opinion of the investigator would compromise patient safety or preclude accurate assessment of outcome.
  • Supraphysiologic doses of glucocorticoids (defined as > 30 mg of hydrocortisone per day or > 7.5 mg of Prednisone per day, or equivalent doses of other agents) or exposure to other immunosuppressive medications in the previous 30 days.
  • Requirement for anticoagulant therapy other than low intensity treatment to maintain patency of central venous catheters.
  • Treatment with antibiotics for proven infection within 1 week prior to study entry or signs and symptoms consistent with an active infection or fever > 38.1 C.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas, M.D. Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

This is a Phase I study designed to evaluate the safety and maximum tolerated dose (MTD) of SGT-94, a novel, tumor-targeted, systemic gene therapy agent for cancer. In addition, we will look for evidence of RB94 expression within tumor tissue after systemic administration of SGT-94.

Read the detailed description

RB94, a tumor suppressor gene, is a modified form of the retinoblastoma gene, RB110. RB94 has shown enhanced tumor suppressor and tumor cell killing activity compared to RB110 in all tumor cell types studied to date, including bladder cancer cell lines. Moreover, RB94 has shown no toxicity to any normal human cells tested.

SGT-94,the agent being tested, is a systemically administered complex composed of the RB94 gene (plasmid DNA)encapsulated in a liposome that is targeted to tumor cells by means of an anti-transferrin receptor single chain antibody fragment (TfRscFv)attached to the outside of the liposome. Pre-clinical in vivo efficacy studies have indicated that SGT-94, when systemically administered, preferentially targets tumor cells and efficiently transfects them. This results in cancer cell death via mechanisms that are unique for RB94 and also increases the tumor's response to conventional radiation and chemotherapy.

This Phase I study is designed to evaluate the safety of SGT-94 and to establish a practically attainable and/or tolerable dose of this anti-cancer agent for use in further clinical trials. Additionally, evidence of RB94 expression within tumor tissue after systemic administration of SGT-94 will be sought, and clinically observable anti-cancer effects in patients will be documented. Enrollment will be targeted to individuals with "RB negative" tumors, i.e. tumors in which there is no staining for RB protein by immunohistochemistry (IHC). Preference will be given to patients with tumors in a location amenable to biopsy following treatment with SGT-94. This would include the prostate, bladder, superficial lymph nodes and any mass suitable for fine needle aspiration under CT or ultrasound guidance, or any lesion reachable by endoscopy.

Conditions
Neoplasm
Being tested
SGT-94
Keywords
neoplasm, bladder cancer, advances solid tumors
Medical subject headings
Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SGT-94Genetic

    SGT-94 will be given at doses of 0.6, 1.2, 2.4, 3.6 and 4.8 mgDNA/infusion(Doses 0-5, respectively)twice weekly for 3 weeks out of 4 in dose levels 0 to 4, and for 5 weeks out of 6 for dose level 5 (also 4.8mg DNA). Intravenous infusion will occur over 1 to 2.5 hours in 5% dextrose,with a final volume of SGT-94 and dextrose of 100 mL to 250 mL, depending on dose level.

Study groups in NCT01517464
Study groupRoleWhat they receive
SGT-94ExperimentalDose escalation of experimental therapeutic SGT-94 to assess safety
Receives: Genetic: SGT-94

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Severity of Adverse Events

    The severity of adverse experiences in each patient will be determined based upon changes in the results of clinical laboratory tests and physical examnations. These findings will be used to determine the safety and tolerability of increasing doses of SGT-94.

    Measured: 4 weeks each patient

Secondary outcomes (3)

  1. Clinical Response

    Clinical Response will be assessed according to standard criteria for the particular solid tumor. In general, Response Evaluation Criteria in Solid Tumors (RECIST) criteria will be used.

    Measured: Week 4

  2. Changes in Tumor Markers

    When appropriate, changes in tumor markers between the values measured at baseline and at week 4 following the cycle of SGT-94 infusion will be assessed.

    Measured: Week 4

  3. Expression of RB94 in Tumor Biopsies

    Tumor targeting and uptake of SGT-94 by the tumor cells will be determined using Immunohistochemistry to assess the expression of RB94 in any tumor biopsies obtained during the study.

    Measured: Week 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionDec 2015
  4. Study completionDec 2015

Resources

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
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01517464
Sponsor's protocol ID
SGT94-01
Acronym
SGT94-01
Status last verified
Apr 2017
First submitted
17 Jan 2012
Last updated
26 Apr 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Pirollo KF, Rait A, Zhou Q, Zhang XQ, Zhou J, Kim CS, Benedict WF, Chang EH. Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo. Clin Cancer Res. 2008 Apr 1;14(7):2190-8. doi: 10.1158/1078-0432.CCR-07-1951.

    PubMed 18381961

  • Xu HJ, Xu K, Zhou Y, Li J, Benedict WF, Hu SX. Enhanced tumor cell growth suppression by an N-terminal truncated retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9837-41. doi: 10.1073/pnas.91.21.9837.

    PubMed 7937901

  • Xu HJ, Zhou Y, Seigne J, Perng GS, Mixon M, Zhang C, Li J, Benedict WF, Hu SX. Enhanced tumor suppressor gene therapy via replication-deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein. Cancer Res. 1996 May 15;56(10):2245-9.

    PubMed 8625292

  • Zhou J, Zhang XQ, Ashoori F, McConkey DJ, Knowles MA, Dong L, Benedict WF. Early RB94-produced cytotoxicity in cancer cells is independent of caspase activation or 50 kb DNA fragmentation. Cancer Gene Ther. 2009 Jan;16(1):13-9. doi: 10.1038/cgt.2008.54. Epub 2008 Jul 25.

    PubMed 18654611

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SGT-94 in people with Neoplasm, run by SynerGene Therapeutics, 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 19 inclusion and 21 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 26 Apr 2017. 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?

Severity of Adverse Events (time frame: 4 weeks each patient). 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 NCT01517464, which also lists 4 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 26 Apr 2017.

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