RetinoblastomaPhase 1AflacST1402NCT02390843
Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
A Phase 1 study testing Simvastatin, Cyclophosphamide and Topotecan in people with Retinoblastoma and Clear Cell Sarcoma, run by Emory University at 1 site in United States.
Trial summary
This is a Phase I trial with new experimental drugs such as simvastatin in combination with topotecan and cyclophosphamide in the hopes of finding a drug that may work against tumors that have come back or that have not responded to standard therapy. Read more about this study
- Who is it for?
- Ages 1 year to 29 years
- Conditions the study is for
- Retinoblastoma, Clear Cell Sarcoma, Renal Cell Carcinoma
- What is being tested?
- Simvastatin, Cyclophosphamide and Topotecan
- Type of treatment
- Pill or oral medicine, 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
- Feb 2015to 22 Sep 2019
- 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 1 year to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects must have had histologic verification of malignancy at original diagnosis or relapse. All subjects with relapsed or refractory solid tumors are eligible including primary or metastatic CNS tumors. In the case of diffuse intrinsic pontine glioma (DIPG), or optic pathway glioma, imaging findings consistent with these tumors will suffice without the need for biopsy for histologic verification.
- Subjects must have either measurable (the presence of at least one lesion that can be accurately measured in at least one dimension with the longest diameter at least 20 mm. With spiral CT scan, lesions must be at least 10 mm.) or evaluable disease (the presence of at least one lesion that cannot be accurately measured in at least one dimension. Such lesions may be evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers or other reliable measures.)
- Subject's current disease state must be one for which there is no known curative therapy.
- Karnofsky ≥ 60% for subjects > 16 years of age and Lansky ≥ 50 for subjects ≤ 16 years of age
- Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
- Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
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- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
- Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
- external beam radiation therapy (XRT): At least 14 days after local palliative XRT (small port); 6 weeks must have elapsed since treatment with therapeutic doses of I131-meta-iodobenzylguanidine (MIBG); At least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT, or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial bone marrow (BM) radiation.
- Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant and 42 days for autologous stem cell infusion after I131-MIBG therapy.
- Subjects must not have received any prior therapy with simvastatin.
- Adequate Bone Marrow Function Defined as:
- For subjects with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) ≥ 750/mm3, Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Subjects with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in a. (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These subjects will not be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent subjects enrolled must be evaluable for hematologic toxicity.
- Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
- Age: 1 to < 2 years; Male and female serum creatinine: 0.6 mg/dL
- 2 to < 6 years; Male and female serum creatinine: 0.8 mg/dL
- 6 to < 10 years; Male and female serum creatinine: 1.0 mg/dL
- 10 to < 13 years; Male and female serum creatinine: 1.2 mg/dL
- 13 to < 16 years; Male serum creatinine: 1.5 mg/dL and female serum creatinine: 1.4 mg/dL
- ≥ 16 years; Male serum creatinine: 1.7 mg/dL and female serum creatinine: 1.4 mg/dL
- Adequate Liver Function Defined as:
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
- serum glutamate pyruvate transaminase (SGPT) or ALT ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
- Adequate Cardiac Function Defined as: corrected QT interval (QTc) ≤ 480 msec
- Normal Creatinine Phosphokinase (CPK) Defined As Not Exceeding Maximum Value:
- Age: 0 to < 4 years; Male and female maximum CPK : 305 units/L
- 4 to < 7 years; Male and female maximum CPK : 230 units/L
- 7 to < 10 years; Male and female maximum CPK : 365 units/L
- 10 to < 12 years; Male maximum CPK: 215 units/L and female maximum CPK: 230 units/L
- 12 to < 14 years; Male maximum CPK: 330 units/L and female maximum CPK: 295 units/L
- 14 to < 16 years; Male maximum CPK: 335 units/L and female maximum CPK: 240 units/L
- 16 to < 19 years; Male maximum CPK: 370 units/L and female maximum CPK: 230 units/L
- ≥ 19 years; Male maximum CPK: 170 units/L and female maximum CPK: 145 units/L
- Willing to sign consent or assent/primary caregiver willing to give consent
Who cannot join
- Pregnancy or breast-feeding
- Concomitant medication dependency including corticosteroids, investigational drugs, anti-cancer agents, anti-graft-versus-host disease (GVHD) agents post-transplant
- subjects who are unable to swallow a tablet or liquid must have a nasogastric (NG) or gastric (G) tube through which the medicine can be administered
- subjects receiving known cytochrome P450 3A4 (CYP3A4) Inhibitors or Inducers
- subjects with uncontrolled infection
- subjects who received prior solid organ transplantation
- subjects with current or previous treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor (any statin)
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta/Emory University
Atlanta, Georgia, 30322
About this study
Official title: A Phase 1 Study Using Simvastatin in Combination With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
This is a Phase I trial with new experimental drugs such as simvastatin in combination with topotecan and cyclophosphamide in the hopes of finding a drug that may work against tumors that have come back or that have not responded to standard therapy. This study will define toxicity of high dose simvastatin in combination with topotecan and cyclophosphamide and evaluate for cholesterol levels and IL6/STAT3 pathway changes as biomarkers of patient response.
Read the detailed description
Chemotherapy resistance is a major cause of treatment failure in pediatric solid tumors. STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that promotes tumor proliferation, metastasis and chemotherapy resistance. Pediatric solid tumors such as neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and central nervous system (CNS) tumors such as glioblastoma and medulloblastoma have aberrant STAT3 signaling. In neuroblastoma, bone marrow production of interleukin 6 (IL-6), a STAT3 activating cytokine, is associated with poor prognosis. Thus STAT3 and its cognate ligand, IL-6, are rational therapeutic targets in pediatric solid and CNS tumors. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, or "statins", lower LDL (low density lipoprotein) cholesterol by inhibiting the rate-limiting step in cholesterol biosynthesis. Pleiotropic properties of statins have been found to not only contribute to lowering the risk of heart disease, but decrease the incidence of cancer as well, leading to their use in clinical trials for adult solid and CNS tumors. Statins have been shown to inhibit IL-6 mediated STAT3 activation to prevent the recruitment of pro-inflammatory cells to injured heart tissue in adult patients. Therefore, the investigators hypothesize that the HMG-CoA reductase inhibitor, simvastatin, will augment chemotherapy effects to improve survival of patients with refractory or relapsed pediatric solid and CNS tumors. This is a Phase I trial of simvastatin in combination with topotecan and cyclophosphamide for refractory and/or relapsed solid or CNS tumors of childhood, in which the investigators will define toxicity and evaluate cholesterol levels and IL6/STAT3 pathway changes as biomarkers of patient response.
- Conditions
- Retinoblastoma, Clear Cell Sarcoma, Renal Cell Carcinoma, Rhabdoid Tumor, Wilms Tumor, Hepatoblastoma
- Being tested
- Simvastatin, Cyclophosphamide, Topotecan, Myeloid growth factor
- Medical subject headings
- Retinoblastoma, Sarcoma, Clear Cell, Carcinoma, Renal Cell, Rhabdoid Tumor, Wilms Tumor, Hepatoblastoma, Neuroblastoma, Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called zocor
The starting dose of simvastatin will be 140 mg/m^2/dose BID for 21 days for the first group. Dose escalation for subsequent groups will be 180 mg/m^2/dose BID, 225 mg/m^2/dose BID, and 290 mg/m^2/dose BID. If the maximum tolerated dose (MTD) has been exceeded at the first dose level, then the subsequent cohort of subjects will be treated at a dose of 100 mg/m2/dose BID (dose level 0). Simvastatin will be administered orally twice daily, approximately 12 hours apart. Feeding tube (nasogastric tube or gastrostomy tube, NOT a jejunum localized tube) administration is allowed. If a subject vomits a dose of simvastatin, it will not be repeated.
CyclophosphamideDrug
Also called Cytoxan, Neosar
The dose of cyclophosphamide will be fixed at 250 mg/m^2/dose. Cyclophosphamide will be administered intravenously over 30 minutes once daily for 5 days every 21 days.
TopotecanDrug
Also called Hycamtin
The dose of topotecan will be fixed at 0.75 mg/m^2/dose. Topotecan will be administered, after cyclophosphamide, intravenously over 30 minutes once daily for 5 days every 21 days.
Myeloid growth factorDrug
Also called Granulocyte colony-stimulating factor (G-CSF), pegylated granulocyte colony-stimulating factor
Myeloid growth factor (G-CSF or pegylated G-CSF) will be initiated 24-48 hours after the completion of topotecan and cyclophosphamide for all subjects, which would be day 6 or 7. Myeloid growth factor should continue until the absolute neutrophil count is greater than 2,000/mm^3
| Study group | Role | What they receive |
|---|---|---|
| simvastatin + topotecan/cyclophosphamide | Experimental | During dose escalation (phase I), standard 3+3 design will be followed. Receives: Drug: Simvastatin; Drug: Cyclophosphamide; Drug: Topotecan; Drug: Myeloid growth factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Simvastatin
MTD will be the maximum dose at which fewer than one-third of subjects experience dose-limiting toxicities (DLTs) during Cycle 1 of therapy.
Measured: First treatment to toxicity (up to 24 months)
Number of Dose-Limiting Toxicities (DLTs)
DLT will be defined as any of the following events that are possibly, probably, or definitely attributable to study drug:
Non-hematological dose-limiting toxicity: Any Grade 3 or 4 non-hematological toxicity (excluding nausea, alanine transaminase (ALT) or aspartate aminotransferase (AST) that returns to baseline or ≤ grade 1 within 7 days of study drug interruption, fever, infection, hypophosphatemia, hypokalemia, hypocalcemia, hypomagnesemia, or creatinine phosphokinase (CPK) elevation that returns to baseline or ≤ grade 1 within 7 days of study drug interruption), Any Grade 2 non-hematological toxicity that persists for ≥ 7 days and is considered sufficiently medically significant or sufficiently intolerable by subjects that it requires treatment interruption, or hematological dose-limiting toxicity, defined as neutropenia or thrombocytopenia that precludes initiation of the next cycle of therapy within 14 days of the scheduled start date.
Measured: Up to 24 months
Secondary outcomes (6)
Percentage of Participants With Overall Tumor Response (Response Rate)
Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions.
Response rate (%) = (number of patients with CR+PR/number of patients)*100
Measured: 24 months
Change in Total Cholesterol Level
Change in serum total cholesterol level after treatment with simvastatin. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Measured: Baseline, 24 months
Change in serum interleukin-6 (IL-6) level
Change in serum interleukin-6 (IL-6) level after treatment with simvastatin. Serum levels of the IL-6 will be assayed using by enzyme-linked immunosorbent assay (ELISA). Higher levels are typically interpreted as worsening of condition.
Measured: Baseline, 24 months
Change in soluble interleukin 6 receptor (sIL-6R)
Change in serum interleukin-6 (IL-6) level after treatment with simvastatin. Serum levels of the sIL-6r will be assayed using by enzyme-linked immunosorbent assay (ELISA). Higher levels are typically interpreted as worsening of condition.
Measured: Baseline, 24 months
Change in signal transducer and activator of transcription 3 (STAT-3) expression
Change in STAT-3 expression after treatment with simvastatin. STAT-3 will be measured using phospho-specific flow cytometry, or phospho-flow.
Measured: Baseline, 24 months
Change in phospho-STAT3 expression
Change in phospho-STAT3 expression after treatment with simvastatin. Phospho-STAT3 expression will be measured using phospho-specific flow cytometry, or phospho-flow.
Measured: Baseline, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study startFeb 2015
- Primary completion22 Sep 2019
- Study completion22 Sep 2019
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 RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Responsible party
- Principal investigator, Kelly Goldsmith, Emory University
- Investigators
- Kelly Goldsmith, MD, Principal investigator, Emory University/Children's Healthcare of Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02390843
- Sponsor's protocol ID
- IRB00078790
- Acronym
- AflacST1402
- Status last verified
- Apr 2020
- First submitted
- 24 Feb 2015
- Last updated
- 3 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Using Simvastatin in Combination With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
- ClinicalTrials.gov ID
- NCT02390843
- Acronym / sponsor ID
- AflacST1402 / IRB00078790
- Conditions
- Retinoblastoma, Clear Cell Sarcoma, Renal Cell Carcinoma, Rhabdoid Tumor, Wilms Tumor, Hepatoblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Study start
- Feb 2015
- Primary completion
- 22 Sep 2019 (actual)
- Study completion
- 22 Sep 2019 (actual)
- First posted
- 18 Mar 2015 (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 trial with new experimental drugs such as simvastatin in combination with topotecan and cyclophosphamide in the hopes of finding a drug that may work against tumors that have come back or that have not responded to standard therapy. This study will define toxicity of high dose simvastatin in combination with topotecan and cyclophosphamide and evaluate for cholesterol levels and IL6/STAT3 pathway changes as biomarkers of patient response.
Detailed description
Chemotherapy resistance is a major cause of treatment failure in pediatric solid tumors. STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that promotes tumor proliferation, metastasis and chemotherapy resistance. Pediatric solid tumors such as neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and central nervous system (CNS) tumors such as glioblastoma and medulloblastoma have aberrant STAT3 signaling. In neuroblastoma, bone marrow production of interleukin 6 (IL-6), a STAT3 activating cytokine, is associated with poor prognosis. Thus STAT3 and its cognate ligand, IL-6, are rational therapeutic targets in pediatric solid and CNS tumors. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, or "statins", lower LDL (low density lipoprotein) cholesterol by inhibiting the rate-limiting step in cholesterol biosynthesis. Pleiotropic properties of statins have been found to not only contribute to lowering the risk of heart disease, but decrease the incidence of cancer as well, leading to their use in clinical trials for adult solid and CNS tumors. Statins have been shown to inhibit IL-6 mediated STAT3 activation to prevent the recruitment of pro-inflammatory cells to injured heart tissue in adult patients. Therefore, the investigators hypothesize that the HMG-CoA reductase inhibitor, simvastatin, will augment chemotherapy effects to improve survival of patients with refractory or relapsed pediatric solid and CNS tumors. This is a Phase I trial of simvastatin in combination with topotecan and cyclophosphamide for refractory and/or relapsed solid or CNS tumors of childhood, in which the investigators will define toxicity and evaluate cholesterol levels and IL6/STAT3 pathway changes as biomarkers of patient response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| simvastatin + topotecan/cyclophosphamide | Experimental | Drug: Simvastatin, Drug: Cyclophosphamide, Drug: Topotecan, Drug: Myeloid growth factorDuring dose escalation (phase I), standard 3+3 design will be followed. |
Who may qualify
- Ages
- 1 year to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (39 listed)
- Subjects must have had histologic verification of malignancy at original diagnosis or relapse. All subjects with relapsed or refractory solid tumors are eligible including primary or metastatic CNS tumors. In the case of diffuse intrinsic pontine glioma (DIPG), or optic pathway glioma, imaging findings consistent with these tumors will suffice without the need for biopsy for histologic verification.
- Subjects must have either measurable (the presence of at least one lesion that can be accurately measured in at least one dimension with the longest diameter at least 20 mm. With spiral CT scan, lesions must be at least 10 mm.) or evaluable disease (the presence of at least one lesion that cannot be accurately measured in at least one dimension. Such lesions may be evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers or other reliable measures.)
- Subject's current disease state must be one for which there is no known curative therapy.
- Karnofsky ≥ 60% for subjects > 16 years of age and Lansky ≥ 50 for subjects ≤ 16 years of age
- Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
Key exclusion criteria (7 listed)
- Pregnancy or breast-feeding
- Concomitant medication dependency including corticosteroids, investigational drugs, anti-cancer agents, anti-graft-versus-host disease (GVHD) agents post-transplant
- subjects who are unable to swallow a tablet or liquid must have a nasogastric (NG) or gastric (G) tube through which the medicine can be administered
- subjects receiving known cytochrome P450 3A4 (CYP3A4) Inhibitors or Inducers
- subjects with uncontrolled infection
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 |
|---|---|---|
| SimvastatinAlso: zocorThe starting dose of simvastatin will be 140 mg/m^2/dose BID for 21 days for the first group. Dose escalation for subsequent groups will be 180 mg/m^2/dose BID, 225 mg/m^2/dose BID, and 290 mg/m^2/dose BID. If the maximum tolerated dose (MTD) has been exceeded at the first dose level, then the subsequent cohort of subjects will be treated at a dose of 100 mg/m2/dose BID (dose level 0). Simvastatin will be administered orally twice daily, approximately 12 hours apart. Feeding tube (nasogastric tube or gastrostomy tube, NOT a jejunum localized tube) administration is allowed. If a subject vomits a dose of simvastatin, it will not be repeated. | Drug | simvastatin + topotecan/cyclophosphamide |
| CyclophosphamideAlso: Cytoxan, NeosarThe dose of cyclophosphamide will be fixed at 250 mg/m^2/dose. Cyclophosphamide will be administered intravenously over 30 minutes once daily for 5 days every 21 days. | Drug | simvastatin + topotecan/cyclophosphamide |
| TopotecanAlso: HycamtinThe dose of topotecan will be fixed at 0.75 mg/m^2/dose. Topotecan will be administered, after cyclophosphamide, intravenously over 30 minutes once daily for 5 days every 21 days. | Drug | simvastatin + topotecan/cyclophosphamide |
| Myeloid growth factorAlso: Granulocyte colony-stimulating factor (G-CSF), pegylated granulocyte colony-stimulating factorMyeloid growth factor (G-CSF or pegylated G-CSF) will be initiated 24-48 hours after the completion of topotecan and cyclophosphamide for all subjects, which would be day 6 or 7. Myeloid growth factor should continue until the absolute neutrophil count is greater than 2,000/mm^3 | Drug | simvastatin + topotecan/cyclophosphamide |
Primary outcome
Maximum Tolerated Dose (MTD) of Simvastatin
Time frame: First treatment to toxicity (up to 24 months)
MTD will be the maximum dose at which fewer than one-third of subjects experience dose-limiting toxicities (DLTs) during Cycle 1 of therapy.
Number of Dose-Limiting Toxicities (DLTs)
Time frame: Up to 24 months
DLT will be defined as any of the following events that are possibly, probably, or definitely attributable to study drug: Non-hematological dose-limiting toxicity: Any Grade 3 or 4 non-hematological toxicity (excluding nausea, alanine transaminase (ALT) or aspartate aminotransferase (AST) that returns to baseline or ≤ grade 1 within 7 days of study drug interruption, fever, infection, hypophosphatemia, hypokalemia, hypocalcemia, hypomagnesemia, or creatinine phosphokinase (CPK) elevation that returns to baseline or ≤ grade 1 within 7 days of study drug interruption), Any Grade 2 non-hematological toxicity that persists for ≥ 7 days and is considered sufficiently medically significant or sufficiently intolerable by subjects that it requires treatment interruption, or hematological dose-limiting toxicity, defined as neutropenia or thrombocytopenia that precludes initiation of the next cycle of therapy within 14 days of the scheduled start date.
6 secondary outcomes
Percentage of Participants With Overall Tumor Response (Response Rate)
Time frame: 24 months
Change in Total Cholesterol Level
Time frame: Baseline, 24 months
Change in serum interleukin-6 (IL-6) level
Time frame: Baseline, 24 months
Change in soluble interleukin 6 receptor (sIL-6R)
Time frame: Baseline, 24 months
Change in signal transducer and activator of transcription 3 (STAT-3) expression
Time frame: Baseline, 24 months
Change in phospho-STAT3 expression
Time frame: Baseline, 24 months
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 3 Apr 2020.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
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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.
Kelly Goldsmith, MD principal investigator
Emory University/Children's Healthcare of Atlanta
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 Simvastatin, Cyclophosphamide and Topotecan in people with Retinoblastoma and Clear Cell Sarcoma, run by Emory University 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 39 inclusion and 7 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 3 Apr 2020. 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?
Maximum Tolerated Dose (MTD) of Simvastatin (time frame: First treatment to toxicity (up to 24 months)). 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 NCT02390843, 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 3 Apr 2020.