A Phase 1/2 Study of AZD1775 (MK-1775) in Combination With Oral Irinotecan in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

Who is this study for? Children, adolescents, and young adults with relapsed or refractory solid tumors
What treatments are being studied? Adavosertib+Irinotecan Hydrochloride
Status: Active, not recruiting
Location: See all (24) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 21
Healthy Volunteers: No
View:

• 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)

• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 2 of every cohort of 3 patients must be evaluable for hematologic toxicity for Part A, 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 1 to < 2 years: 0.6 mg/dL

• Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females)

• Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females)

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

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

• Serum albumin >= 2 g/dL

• Correct QT interval (QTc) =< 480 msec; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause torsades de pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available

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

• Nervous system disorders (Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0]) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible

• 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

• Tissue blocks or slides must be sent if available, with exclusions; if tissue blocks or slides are unavailable, the study chair must be notified prior to study enrollment

• Patients must be able to swallow capsules

Locations
United States
Alabama
Children's Hospital of Alabama
Birmingham
California
Children's Hospital Los Angeles
Los Angeles
Children's Hospital of Orange County
Orange
UCSF Medical Center-Mission Bay
San Francisco
UCSF Medical Center-Parnassus
San Francisco
Colorado
Children's Hospital Colorado
Aurora
Washington, D.c.
Children's National Medical Center
Washington
Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta
Illinois
Lurie Children's Hospital-Chicago
Chicago
Indiana
Riley Hospital for Children
Indianapolis
Massachusetts
Dana-Farber Cancer Institute
Boston
Michigan
C S Mott Children's Hospital
Ann Arbor
Minnesota
University of Minnesota/Masonic Cancer Center
Minneapolis
Missouri
Washington University School of Medicine
Saint Louis
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati
Oregon
Oregon Health and Science University
Portland
Pennsylvania
Children's Hospital of Philadelphia
Philadelphia
Children's Hospital of Pittsburgh of UPMC
Pittsburgh
Tennessee
Saint Jude Children's Research Hospital
Memphis
Texas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston
Washington
Seattle Children's Hospital
Seattle
Wisconsin
Children's Hospital of Wisconsin
Milwaukee
Other Locations
Canada
Hospital for Sick Children
Toronto
Time Frame
Start Date: March 27, 2014
Estimated Completion Date: December 31, 2022
Participants
Target number of participants: 76
Treatments
Experimental: Treatment (irinotecan hydrochloride, adavosertib)
Patients receive irinotecan hydrochloride PO and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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