Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors
Neuroblastoma, Rhabdomyosarcoma, Ewing's Sarcoma
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring Neuroblastoma, Rhabdomyosarcoma, Soft Tissue, Pediatric Oncology, Abraxane, albumin-bound paclitaxel, nab-paclitaxel, ABI-007, taxane, solid tumors
Eligibility Criteria
Inclusion Criteria:
Patients must meet all of the following criteria to be enrolled in the study:
Patient has a confirmed solid tumor diagnosis according to the
following:
Phase 1: patient has a recurrent or refractory solid tumor that has
progressed or did not respond to standard therapy, or for which no
standard anticancer therapy exists
- Phase 2: patient has radiologically documented measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for neuroblastoma, evaluable disease by 123^I-metaiodobenzylguanidine [MIBG]/Curie score is also acceptable) in 1 of the following tumor types and has failed up to 3 lines of treatment: Group 1: neuroblastoma, Group 2: rhabdomyosarcoma; Group 3: Ewing's sarcoma.
- The patient has a Lansky/Karnofsky performance status score of ≥ 70%.
The patient has adequate serum chemistry levels, evidenced by the
following laboratory values
aspartate aminotransferase (AST)/serum glutamic-oxaloacetric
transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic
pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN)
- Total bilirubin ≤ 1.5 × ULN
- Creatinine ≤ 1.5 × ULN
The patient has adequate bone marrow function, evidenced by the
following:
- Absolute neutrophil count ≥ 1.0 × 10^9 cells/L
Platelets ≥ 80 × 10^9 cells/L (transfusion independent, defined as not
receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10^9 cells/L
- Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion).
The patient (when applicable) or patient's parent(s) or legal guardian(s)
understand(s) and voluntarily signed an informed consent document prior
to any study-related assessments/procedures being conducted. Where
locally applicable, the patient also understands and voluntarily provides
his/her assent prior to any study-related assessments/procedures being
conducted.
Male patients of childbearing potential must use a condom during
sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication.
Female patients of childbearing potential [defined as all female
patients ≥ 12 years old or who have reached menarche, whichever occurs
first] must have both of the following:
a. Agree to the use of two physician-approved contraceptive methods
simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations.
i. True abstinence: When this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, postovulation methods) and withdrawal are not
acceptable methods of contraception.
ii. Acceptable contraceptive methods include: oral, injectable, or
implantable hormonal contraceptive; tubal ligation; intra-uterine device;
barrier contraceptive with spermicide; or vasectomized partner) including
at least one barrier method.
b. Have negative serum pregnancy test result at screening confirmed by
negative urine pregnancy dipstick within 72 hours prior to first dose of
investigational product (if serum test occurred > 72 hours from first
dose); pregnancy test with sensitivity of at least 25 mIU/mL.
Exclusion Criteria:
- The presence of any of the following will exclude a patient from enrollment:
- The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for > 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis.
- The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product.
- The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product.
- The patient has received any investigational therapy ≤ 28 days prior to start of investigational product. Investigational therapy is defined as any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric.
- The patient has received any biological therapy ≤ 7 days prior to the start of investigational product, or monoclonal antibody ≤ 3 half-lives or 28 days, whichever is shorter, prior to the first dose of investigational product.
- The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product.
- The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product.
- The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma.
- The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy).
- The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis.
- The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status.
- The patient has an uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- The patient has any condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk if he/she were to participate in the study.
- The patient has any condition that confounds the ability to interpret data from the study.
- The patient or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator.
- The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.
Sites / Locations
- Phoenix Childrens Hospital
- Columbia University Medical Center
- The Hospital for Sick Children
- Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center
- Hopital d'Enfants, CHU Nancy
- Institut Curie
- Institut Gustave Roussy
- Azienda Ospedaliera Universitaria Meyer
- Children's Hospital Largo
- Istituto Nazionale Tumori
- Clinica di Oncoematologia
- Policlinico Agostino Gemelli
- l'Azienda Ospedaliera Regina Margherita - Sant Anna
- Hospital Universitario Vall D Hebron
- Hospital Sant Joan de Deu
- Spanish National Cancer Research Centre
- Hospital Universitario Virgen Del Rocio
- Unidad de Oncologia Pediatrica, Hospital Universitario la Fe
- Universitäts-Kinderklinik
- Royal Marsden Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
nab-paclitaxel
Phase 1: Nab-Paclitaxel 120 mg/m^2
Phase 1: Nab-Paclitaxel 150 mg/m^2
Phase 1: Nab-Paclitaxel 180 mg/m^2
Phase 1: Nab-Paclitaxel 210 mg/m^2
Phase 1: Nab-Paclitaxel 240 mg/m^2
Phase 1: Nab-Paclitaxel 270 mg/m^2
Phase 2: Ewing's Sarcoma
Phase 2: Neuroblastoma
Phase 2: Rhabdomyosarcoma
nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
nab-paclitaxel 120 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.