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Solid TumorPhase 1NCT01683149

Sorafenib and Topotecan in Refractory/Recurrent Pediatric Malignancies

A Phase 1 study testing Topotecan and Sorafenib in people with Solid Tumor, run by H. Lee Moffitt Cancer Center and Research Institute at 9 sites 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

H. Lee Moffitt Cancer Center and Research Institute will be the Sunshine Project Coordinator, but will not be recruiting locally. The purpose of this research study is to establish a dose of the combination of drugs, Topotecan and Sorafenib in children. This will be called the maximum tolerated dose. Read more about this study

Who is it for?
Ages 3 to 18 years
Conditions the study is for
Solid Tumor
What is being tested?
Topotecan and Sorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
9 sitesUnited States
Study dates
Jan 2013to Jan 2016
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 3 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Life expectancy of at least 12 weeks (3 months)
  • Must have had relapsed or refractory solid tumor malignancy, or a relapsed or refractory central nervous system malignancy AND must have received at least one prior course of therapy for their malignancy.
  • Patients with a solid tumor must have radiographic evidence of disease. Bone only disease is acceptable if biopsy proven but will not be eligible for response criteria by RECIST 1.1. Ideally patients will have disease evaluable by RECIST 1.1.
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
  • Karnofsky ≥ 50 for patients > 16 years of age, and Lansky ≥ 50 for patients ≤ 16 years of age.
  • Prior Therapy: Patients with solid tumors must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
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  • Previous Sorafenib or Topotecan: Patients may not have previously been treated with sorafenib. Patients may have been previously treated with topotecan provided it was in combination with other agents and the most recent dose was more than 6 months from study entry. Patients in whom disease has progressed on single agent topotecan will not be eligible for this study.
  • Myelosuppressive Chemotherapy: Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks or nitrosourea within 6 weeks of entry onto this study.
  • Hematopoietic Growth Factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.
  • Biologic (anti-neoplastic agent): At least 21 days or 5 half lives (whichever is greater duration) since the completion of therapy with 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.
  • Radiation Therapy (XRT): ≥ 4 wks for local palliative XRT (small port); ≥ 3 months must have elapsed if prior TBI, or craniospinal XRT or if ≥ 50% radiation of pelvis; ≥ 6 weeks must have elapsed if other substantial bone marrow (BM) radiation.
  • Stem Cell Transplant or Rescue without total body irradiation (TBI): For allograft: no evidence of active graft vs. host disease and ≥ 3 months must have elapsed since stem cell transplantation (SCT). Autologous transplant recipients must be transfusion independent and not require growth factors for >4 weeks.
  • All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate will be obtained according to local Institutional Review Board (IRB) guidelines. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
  • Organ Function Requirements - Adequate Bone Marrow Function Defined As:
  • Peripheral absolute neutrophil count (ANC) ≥ 1500/μL.
  • Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • Hemoglobin ≥ 10.0 gm/dL (may receive red blood cell transfusions)
  • Patients with known bone marrow metastatic disease will be eligible for study. These patients must not be known to be refractory to red cell or platelet transfusion. If dose limiting hematologic toxicity is observed, all subsequent patients enrolled at the dose level must not have bone marrow metastatic disease.
  • Adequate Renal Function Defined As: Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or serum creatinine based on age/gender as defined in the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).
  • Adequate Liver Function Defined As:
  • Bilirubin (sum of conjugated + unconjugated) ≤ upper limit of normal (ULN) for age
  • Alanine transaminase (ALT) ≤ upper limit of normal for age
  • All clinically significant chemistries excluding alkaline phosphatase, uric acid, aspartic transaminase (AST) and lactate dehydrogenase (LDH) must be grade 1 or less
  • Adequate Cardiac Function Defined As:
  • Normal 12 lead EKG with corrected QT interval (QTc) < 450 msec, and either:
  • Shortening fraction ≥ 28% or left ventricular ejection fraction ≥ 50%.
  • Systolic Blood Pressure and Diastolic Blood Pressure ≤ 95th percentile for age and gender
  • Adequate Pulmonary Function Defined As: No evidence of dyspnea at rest, and a resting pulse oximetry > 92%.
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of enrollment, signing the Informed Consent Form (ICF).
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
  • Prothrombin time-international normalized ratio (PT-INR) ≤ 1.5 X ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN.
  • Participants (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug.
  • Must be able to swallow and retain oral medication

Who cannot join

  • Previous assignment to treatment during this study
  • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management
  • Evidence or history of bleeding diathesis or coagulopathy
  • Any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4 weeks of treatment; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 3 or higher within 4 weeks of treatment
  • Have used strong cytochrome P450 3A4 (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before treatment
  • Any previously untreated or concurrent cancer that is distinct in primary site or histology from the primary. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form)
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  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • History of organ allograft. (Including corneal transplant)
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
  • Women who are pregnant or breast-feeding
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments
  • Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Florida, Gainesville

    Gainesville, Florida, 32610

  • Connecticut Childrens Medical Center

    Hartford, Connecticut, 06106

  • Nemours Children's Clinic, Jacksonville

    Jacksonville, Florida, 32207

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Miami, Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Primary Children's Medical Center/Utah

    Salt Lake City, Utah, 84113

  • All Children's Hospital, St. Petersburg

    St. Petersburg, Florida, 33701

  • Montefiore Medical Center, Children's Hospital at Montefiore

    The Bronx, New York, 10467

  • Nemours/Alfred I. duPont Hospital for Children, Delaware

    Wilmington, Delaware, 19803

Other trials in United States

About this study

Official title: Phase I, Traditional 3+3, Trial of PO Sorafenib and Topotecan in Refractory or Recurrent Pediatric Solid Malignancies

  1. Lee Moffitt Cancer Center and Research Institute will be the Sunshine Project Coordinator, but will not be recruiting locally.

The purpose of this research study is to establish a dose of the combination of drugs, Topotecan and Sorafenib in children. This will be called the maximum tolerated dose. The chemotherapy in this study is a combination of Topotecan and Sorafenib. The investigators are trying to find the highest dose of Topotecan and Sorafenib that can be given safely to children with Refractory or Recurrent Pediatric Solid Malignancies. The investigators will do this by testing different doses of these drugs in different groups of children. The investigators will also study how the body processes these drugs.

Conditions
Solid Tumor
Being tested
Topotecan, Sorafenib
Keywords
Refractory, Relapsed, Recurrent, Pediatric, Malignancy
Medical subject headings
Recurrence, Neoplasms

What participants receive

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

  • TopotecanDrug

    Also called Topoisomerase-I inhibitor

    Topotecan will be given by mouth as outlined in treatment arm.

  • SorafenibDrug

    Also called BAY 43-9006

    Sorafenib will be given by mouth as outlined in treatment arm.

Study groups in NCT01683149
Study groupRoleWhat they receive
Combination ChemotherapyExperimentalCombination Chemotherapy: Topotecan and Sorafenib. Participants will receive the treatment in cycles. Every cycle is 28 days long. For the first cycle participants will get the chemotherapy drugs: * Topotecan PO (by mouth) once daily on days 1-5 and days 8-12 * Sorafenib PO (by mouth) twice daily (BID), continuously on days 2-28 of cycle one and days 1-28 on each additional cycle. * Level -1: Topotecan 1.0 mg/m^2: Sorafenib 100 mg/m^2 BID * Level -2: Topotecan 0.8 mg/m^2: Sorafenib 100 mg/m^2 BID * Level 1: Topotecan 1.0 mg/m^2: Sorafenib 150 mg/m^2 BID * Level 2: Topotecan 1.4 mg/m^2: Sorafenib 150 mg/m^2 BID * Level 3: Topotecan 1.4 mg/m^2: Sorafenib 200 mg/m^2 BID * Level 4: Topotecan 1.8 mg/m^2: Sorafenib 200 mg/m^2 BID
Receives: Drug: Topotecan; Drug: Sorafenib

What is being measured

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

  1. Maximum Tolerated Dose (MTD)

    Establish the recommended phase II dose of the combination of topotecan and sorafenib in children. This will be the maximum tolerated dose.

    Measured: 24 months

Secondary outcomes (2)

  1. Time to Progression (TTP)

    Determine Time to Progression (TTP) for all patients, comparing TTP on study to TTP on previous regimen. This study will use the (RECIST 1.1) Response Evaluation Criteria in Solid Tumors from the NCI for assessment of radiographic response in patients with solid tumors and in order to determine if patients have met off study criteria, i.e. disease progression. Progressive Disease (PD): At least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions, or evidence of laboratory or clinical progression.

    Measured: 24 months

  2. The Number of Participants with Adverse Events as a Measure of Safety and Feasibility

    Describe the toxicity as per NCI Common Toxicity Criteria, version 4.0 (CTCAE 4.0).

    Measured: 24 months

Timeline

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

  1. First posted11 Sep 2012 (estimated)
  2. Study startJan 2013
  3. Primary completionJan 2016
  4. Study completionJan 2016

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
NCT01683149
Sponsor's protocol ID
MCC-16963
Other IDs
ONC-2011-49, Sunshine Project 002
Status last verified
Mar 2016
First submitted
7 Sep 2012
Last updated
4 Mar 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Topotecan and Sorafenib in people with Solid Tumor, run by H. Lee Moffitt Cancer Center and Research Institute at 9 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 33 inclusion and 12 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 4 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 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?

Maximum Tolerated Dose (MTD) (time frame: 24 months). 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 NCT01683149.

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 4 Mar 2016.

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