Sorafenib and Topotecan in Refractory/Recurrent Pediatric Malignancies

NCT01683149 | Completed Phase 1

• 3 other identifiers: MCC-16963ONC-2011-49Sunshine Project 002
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 9

Brief 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. 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

Keywords

Refractory; Relapsed; Recurrent; Pediatric; Malignancy

Outcome Measures

Primary Outcomes (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.

  24 months

Secondary Outcomes (2)

• Time to Progression (TTP)

  24 months

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

  24 months

Study Arms (1)

Combination Chemotherapy

EXPERIMENTAL

Combination 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

Drug: Topotecan; Drug: Sorafenib

Interventions

Topotecan DRUG

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

Also known as: Topoisomerase-I inhibitor

Combination Chemotherapy

Sorafenib DRUG

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

Also known as: BAY 43-9006

Combination Chemotherapy

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Pediatric Cancer Foundation: collaborator
• Bayer: collaborator

Study Sites (9)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Connecticut Childrens Medical Center

Hartford, Connecticut, 06106, United States

Location

Nemours/Alfred I. duPont Hospital for Children, Delaware

Wilmington, Delaware, 19803, United States

Location

University of Florida, Gainesville

Gainesville, Florida, 32610, United States

Location

Nemours Children's Clinic, Jacksonville

Jacksonville, Florida, 32207, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

All Children's Hospital, St. Petersburg

St. Petersburg, Florida, 33701, United States

Location

Montefiore Medical Center, Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Primary Children's Medical Center/Utah

Salt Lake City, Utah, 84113, United States

Location

MeSH Terms

Conditions

Recurrence; Neoplasms

Interventions

Topotecan; Topoisomerase I Inhibitors; Sorafenib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents; Therapeutic Uses; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Damon Reed, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• G. Douglas Letson, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 11, 2012
• Study Start: January 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: March 4, 2016

Record last verified: 2016-03

Locations

US (9)