Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors

Completed · Phase 1/Phase 2

Conditions studied: Central Nervous System Embryonal Tumor With Rhabdoid Features, Central Nervous System Embryonal Tumor, Not Otherwise Specified, Central Nervous System Ganglioneuroblastoma, Embryonal Tumor With Multilayered Rosettes, C19MC-Altered, Pineoblastoma, Primary Central Nervous System Neoplasm, Recurrent Childhood Central Nervous System Embryonal Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Rhabdomyosarcoma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Rhabdomyosarcoma

In brief

This phase I/II trial studies the side effects and best dose of adavosertib and irinotecan hydrochloride in treating younger patients with solid tumors that have come back (relapsed) or that have not responded to standard therapy (refractory). Adavosertib and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT02095132

Run by

National Cancer Institute (NCI)

People needed

76

Starts

2014-03-28

Expected to finish

2023-06-30

Last updated by the study team

2023-09-26

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)
• Part A: Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors
• Part B: Patients with relapsed or refractory neuroblastoma
• Part C: Patients with relapsed or refractory medulloblastoma or CNS embryonal tumors formally classified as PNET (pineoblastoma, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes, medulloepithelioma, CNS embryonal tumor with rhabdoid features [INI1 intact] and CNS embryonal tumor, not otherwise specified)
• Part D: Patients with relapsed or refractory rhabdomyosarcoma
• Part A: Patients must have a body surface area >= 0.35 m\^2 at the time of study enrollment if enrolling on dose levels 1-5; patients must have a body surface area >= 0.46 m\^2 at the time of study enrollment if enrolling on dose level 0
• Parts B, C, and D: Phase 2 Expansion: Patients must have a body surface area of > 0.49 m\^2 at the time of study enrollment at the recommended phase 2 dose of AZD-1775
• Part A: Patients must have either measurable or evaluable disease
• Part B: Patients must have either measurable disease or must be evaluable for MIBG response without evidence of Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesions; patients with neuroblastoma in bone marrow only are not eligible
• Part C: Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
• Part D: Patients must have measurable disease for Part D
• 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; 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 chemotherapy
• At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
• At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) 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
• 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
• At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• >= 21 days must have elapsed from infusion of lase dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior traumatic brain injury (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow radiation, including therapeutic doses of iobenguane (MIBG)
• Stem cell Infusion without TBI: no evidence of active graft vs host disease and at least 84 days must have elapsed after transplant or stem cell infusion
• Patients previously treated with irinotecan are eligible for this study
• For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/mm\^3
• For patients with solid tumors without known bone marrow involvement: platelet count >= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

You may not qualify if…

• Pregnant or breast-feeding women may not be entered on this study as there is yet no available information regarding human fetal or teratogenic toxicities; 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 double barrier contraceptive method for the entire duration of protocol therapy and for 3 months (males) and 1 month (females) after study drug discontinuation
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
• 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 currently receiving drugs that are strong or moderate inhibitors and/or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible; the use of aprepitant as an antiemetic is prohibited due to early drug interaction data demonstrating increased exposure to AZD1775 (MK-1775); caution should be exercised with concomitant administration of AZD1755 (MK-1775) and agents that are sensitive substrates of cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), 2C9 and 2C19, or substrates of this enzyme with narrow therapeutic ranges, as well as agents that are inhibitors or substrates of permeability glycoprotein (P-gp)
• 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 14 days prior to enrollment
• Patients with cardiac diseases ongoing or in the past 6 months (e.g. congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias) are not eligible for this trial
• 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
• Patients with a history of allergic reaction to irinotecan, cephalosporins or a severe penicillin allergy are not eligible
• Patients unable to swallow capsules whole are not eligible; nasogastric or gastric (G) tube administration is not allowed

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• UCSF Medical Center-Mission Bay — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta - Egleston — Atlanta, Georgia, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States
• University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States
• Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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