Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors
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
3 other identifiers
interventional
76
2 countries
24
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2014
CompletedFirst Posted
Study publicly available on registry
March 24, 2014
CompletedStudy Start
First participant enrolled
March 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2020
CompletedResults Posted
Study results publicly available
October 5, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2023
CompletedSeptember 26, 2023
August 1, 2023
6.8 years
March 13, 2014
February 8, 2022
September 1, 2023
Conditions
Outcome Measures
Primary Outcomes (6)
Maximum Tolerated Dose (MTD)
MTD is defined as the maximum doses of adavosertib and irinotecan hydrochloride at which fewer than one-third of patients experience dose limiting toxicities when receiving this combination.
Up to 21 days
Number of Participants With Cycle 1 DLT
To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
Up to 21 days
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, AUC
The PK parameters will be summarized by means and standard deviations
Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Cmax
The PK parameters will be summarized by means and standard deviations
Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, HL-Lambda (Half Life)
The PK parameters will be summarized by means and standard deviations
Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Tmax
The PK parameters will be summarized by means and standard deviations
Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Secondary Outcomes (3)
Number and Percentage of Participants With Best Overall Response With Partial or Complete Response
Up to 1 year
Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells
Up to 1 day
Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification
Assessed at Baseline
Study Arms (1)
Treatment (irinotecan hydrochloride, adavosertib)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given PO
Eligibility Criteria
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)
- +26 more criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Kristina A Cole
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2014
First Posted
March 24, 2014
Study Start
March 28, 2014
Primary Completion
December 31, 2020
Study Completion
June 30, 2023
Last Updated
September 26, 2023
Results First Posted
October 5, 2022
Record last verified: 2023-08