Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

Status: Recruiting
Phase:
DFCI Protocol ID: 17-728

This phase I trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin when given together with temozolomide and irinotecan hydrochloride in treating pediatric patients with solid tumors that have come back after a period of time during which the tumor could not be detected or has not responded to treatment. Nanoparticle albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may work better in treating pediatric patients with solid tumors.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Steven Dubois MD, Dana Farber Cancer Institute

Site-responsible Investigators:

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Patients must have a body surface area (BSA) of >= 0.2 m^2 at the time of study
     enrollment

  -  Patients with recurrent or refractory solid tumors, including CNS tumors, are
     eligible; patients must have had histologic verification of malignancy at original
     diagnosis or relapse except in patients with intrinsic brain stem tumors, optic
     pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid
     (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic
     gonadotropin (HCG)

  -  Patients must have either measurable or evaluable disease

  -  Patient's current disease state must be one for which there is no known curative
     therapy

  -  Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
     years of age

       -  Note: Neurologic deficits in patients with CNS tumors must have been relatively
  stable for at least 7 days prior to study enrollment; patients who are unable to
  walk because of paralysis, but who are up in a wheelchair, will be considered
  ambulatory for the purpose of assessing the performance score

  -  Patients must have fully recovered from the acute toxic effects of all prior
     anti-cancer therapy and must meet the following minimum duration from prior
     anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
     numerical eligibility criteria are met, e.g. blood count criteria, the patient is
     considered to have recovered adequately

  -  Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the
     duration of this interval must be discussed with the study chair and the
     study-assigned research coordinator prior to enrollment

       -  >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
  days if prior nitrosourea)

  -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced
     platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of
     agent; the duration of this interval must be discussed with the study chair and the
     study-assigned research coordinator prior to enrollment

  -  Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and
     toxicity related to prior antibody therapy must be recovered to grade =< 1

  -  Corticosteroids: If used to modify immune adverse events related to prior therapy, >=
     14 days must have elapsed since last dose of corticosteroid

  -  Hematopoietic growth factors: >= 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 and the
     study-assigned research coordinator

  -  Interleukins, interferons and cytokines (other than hematopoietic growth factors): >=
     21 days after the completion of interleukins, interferon or cytokines (other than
     hematopoietic growth factors)

  -  Stem cell infusions (with or without total body irradiation [TBI]):

       -  Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell
  infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days
  after infusion, and no evidence of graft-versus-host disease (GVHD)

       -  Autologous stem cell infusion including boost infusion: >= 42 days

  -  Cellular therapy: >= 42 days after the completion of any type of cellular therapy
     (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)

  -  X ray (XRT)/external beam irradiation including protons: >= 14 days after local XRT;
     >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42
     days if other substantial bone marrow (BM) radiation

  -  Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine
     metaiodobenzylguanidine [131I-MIBG]): >= 42 days after systemically administered
     radiopharmaceutical therapy

  -  Irinotecan, temozolomide and mammalian target of rapamycin (mTOR) inhibitor exposure:

       -  Patients who have received prior single agent therapy with irinotecan,
  temozolomide, or an mTOR inhibitor, excluding ABI-009, are eligible

       -  Patients who have received prior combination therapy with two of the three
  agents, excluding ABI-009, are eligible

       -  Patients who have received prior therapy with all three agents in combination
  (i.e. irinotecan, temozolomide, and an mTOR inhibitor) are not eligible

       -  Patients who have previously received irinotecan and temozolomide and had
  significant toxicity with these two drugs are not eligible

  -  For patients with solid tumors without known bone marrow involvement:

       -  Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

       -  Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
  platelet transfusions for at least 7 days prior to enrollment)

       -  Hemoglobin >= 8.0 g/dl at baseline (may receive red blood cell [RBC]
  transfusions)

  -  Patients with known bone marrow metastatic disease will be eligible for the study if
     they meet the following criteria: Peripheral absolute neutrophil count (ANC) >=
     750/mm^3 Platelet count >= 50,000/mm^3 (may receive transfusions provided they are not
     known to be refractory to red cell or platelet transfusions); Hemoglobin >= 8.0 g/dL
     at baseline (may receive RBC transfusions, provided they are not known to be
     refractory to RBC transfusions); These patients will not be evaluable for hematologic
     toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic
     toxicity for the dose-escalation part of the study; if dose-limiting hematologic
     toxicity is observed, all subsequent patients enrolled must be evaluable for
     hematologic toxicity

  -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
     ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

       -  Age: maximum serum creatinine (mg/dL)

       -  1 to < 2 years: 0.6 (male and female)

       -  2 to < 6 years: 0.8 (male and female)

       -  6 to < 10 years: 1 (male and female)

       -  10 to < 13 years: 1.2 (male and female)

       -  13 to < 16 years: 1.5 (male), 1.4 (female)

       -  >= 16 years: 1.7 (male), 1.4 (female)

  -  Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
     age

  -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =<3 x
     ULN=135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

  -  Serum albumin >= 2 g/dL

  -  Pulse oximetry > 94% on room air if there is clinical indication for determination
     (e.g. dyspnea at rest)

  -  Patients with seizure disorder may be enrolled if on non-enzyme inducing
     anticonvulsants and well controlled

  -  Nervous system disorders (National Cancer Institute Common Terminology Criteria for
     Adverse Events [NCI CTCAE]) resulting from prior therapy must be =< grade 2

  -  Serum triglyceride level =< 300 mg/dL

  -  Serum total cholesterol level =< 300 mg/dL

  -  Random or fasting blood glucose =< the upper normal limits for age; if the initial
     blood glucose is a random sample that is outside of the normal limits, then follow-up
     fasting blood glucose can be obtained and must be =< the upper normal limits for age

  -  International normalized ratio (INR) =< 1.5

  -  Not currently receiving anticoagulation therapy

  -  All patients and/or their parents or legally authorized representatives must sign a
     written informed consent; assent, when appropriate, will be obtained according to
     institutional guidelines

Exclusion Criteria:

  -  Pregnant or breast-feeding women will not be entered on this study; pregnancy tests
     must be obtained in girls who are post-menarchal; males or females of reproductive
     potential may not participate unless they have agreed to use an effective
     contraceptive method both during and for 6 months after participation in this study;
     abstinence is an acceptable method of contraception

  -  Patients receiving corticosteroids must have been on a stable or decreasing dose of
     corticosteroid for at least 7 days prior to enrollment; if used to modify immune
     adverse events related to prior therapy, >= 14 days must have elapsed since last dose
     of corticosteroid

  -  Patients who are currently receiving another investigational drug are not eligible

  -  Patients who are currently receiving other anti-cancer agents are not eligible

  -  Patients who are receiving cyclosporine, tacrolimus or other agents to prevent
     graft-versus-host disease post bone marrow transplant are not eligible for this trial

  -  Patients must not have received enzyme-inducing anticonvulsants for at least 7 days
     prior to enrollment

  -  Patients who are currently receiving therapeutic anticoagulants (including aspirin,
     low molecular weight heparin, and others) are not eligible

  -  Patients must not be receiving any strong CYP3A4 or P-glycoprotein (P-gp) inducers or
     inhibitors within 7 days prior to enrollment; moderate inducers or inhibitors of
     CYP3A4 and P-gp should also be avoided during ABI-009 treatment, if possible

  -  Patients with interstitial lung disease and/or pneumonitis are not eligible

  -  Patients with a history of allergic reactions attributed to compounds of similar
     composition, including macrolide and ketolide antibiotics, temsirolimus/other mTOR
     inhibitors, temozolomide or irinotecan are not eligible

  -  Patients with hypersensitivity to albumin are not eligible

  -  Patients who have had or are planning to have the following invasive procedures are
     not eligible:

       -  Major surgical procedure, laparoscopic procedure, open biopsy or significant
  traumatic injury within 28 days prior to enrollment

       -  Subcutaneous port placement or central line placement is not considered major
  surgery; external central lines must be placed at least 3 days prior to
  enrollment and subcutaneous ports must be placed at least 7 days prior to
  enrollment

       -  Core biopsy within 7 days prior to enrollment

       -  Fine needle aspirate within 7 days prior to enrollment

       -  NOTE: For purposes of this study, bone marrow aspirate and biopsy are not
  considered surgical procedures and therefore are permitted within 14 days prior
  to start of protocol therapy

  -  Patients with current deep vein thrombosis or deep vein thrombosis within the past 6
     months are not eligible

  -  Patients who have an uncontrolled infection are not eligible

  -  Patients who have received a prior solid organ transplantation are not eligible

  -  Patients who in the opinion of the investigator may not be able to comply with the
     safety monitoring requirements of the study are not eligible

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