Central Nervous System Embryonal Tumor With Rhabdoid FeaturesPhase 1/2NCT02095132
Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors
A Phase 1/2 study testing Adavosertib and Irinotecan Hydrochloride in people with Central Nervous System Embryonal Tumor With Rhabdoid Features and Central Nervous System Embryonal Tumor, Not Otherwise Specified, run by National Cancer Institute (NCI) at 24 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Central Nervous System Embryonal Tumor With Rhabdoid Features, Central Nervous System Embryonal Tumor, Not Otherwise Specified, Central Nervous System Ganglioneuroblastoma
- What is being tested?
- Adavosertib and Irinotecan Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 28 Mar 2014to 30 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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 2 to < 6 years: 0.8 mg/dL
- Age 6 to < 10 years: 1 mg/dL
- Age 10 to < 13 years: 1.2 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States23 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Hospital Los Angeles
Los Angeles, California, 90027
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
UCSF Medical Center-Parnassus
San Francisco, California, 94143
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: 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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of adavosertib (AZD1755 [MK-1775]) administered on days 1 through 5 every 21 days, in combination with oral irinotecan (irinotecan hydrochloride), to children with recurrent or refractory solid tumors.
II. To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
III. To characterize the pharmacokinetics of AZD1755 (MK-1775) in children with refractory cancer.
SECONDARY OBJECTIVES:
- To preliminarily define the antitumor activity of AZD1755 (MK-1775) and irinotecan within the confines of a Phase 1 study.
II. To obtain initial phase 2 efficacy data on the anti-tumor activity of AZD1755 (MK-1775) in combination with irinotecan administered to children with relapsed or refractory neuroblastoma, in children with relapsed or refractory medulloblastoma/CNS PNET (central nervous system primitive neuroectodermal tumor) and in children with relapsed or refractory rhabdomyosarcoma.
III. To investigate checkpoint over-ride by AZD1755 (MK-1775) via the mechanism-based pharmacodynamic (PD) biomarker of decreased cyclin-dependent kinase 1 (CDK1) phosphorylation in correlative and exploratory studies.
IV. To evaluate potential predictive biomarkers of AZD1755 (MK-1775) sensitivity, including v-myc avian myelocytomatosis viral oncogene homolog (MYC), v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), phosphorylated-WEE1 G2 checkpoint kinase (p-Wee1), enhancer of zeste homolog 2 (Drosophila) (EZH2) and gamma-H2A histone family, member gamma-(H2AX) in tumor tissues in correlative and exploratory studies.
OUTLINE: This is a phase I, dose-escalation followed by a phase II study.
Patients receive irinotecan hydrochloride orally (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.
After completion of study treatment, patients are followed up periodically.
- Conditions
- 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
- Being tested
- Adavosertib, Irinotecan Hydrochloride
- Medical subject headings
- Neuroectodermal Tumors, Primitive, Pinealoma, Central Nervous System Neoplasms, Medulloblastoma, Neuroblastoma, Rhabdomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdavosertibDrug
Also called AZD-1775, AZD1775, MK-1775, MK1775
Given PO
Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (irinotecan hydrochloride, adavosertib) | Experimental | 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. Receives: Drug: Adavosertib; Drug: Irinotecan Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Frequency (%) of response-evaluable patients with best overall response of partial or complete response as determined by revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Measured: Up to 1 year
Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells
Mean (SD) of the increase in gamma H2AX at 4 hours versus baseline among patients in Part A stratified by dose level.
Measured: Up to 1 day
Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification
Frequency (%) of Part B Neuroblastoma participants with MYCN amplification.
Measured: Assessed at Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2014 (estimated)
- Study start28 Mar 2014
- Primary completion31 Dec 2020
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Central Nervous System Embryonal Tumor With Rhabdoid FeaturesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kristina A Cole, Principal investigator, COG Phase I Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02095132
- Sponsor's protocol ID
- NCI-2014-00547
- Other IDs
- NCI-2014-00547, ADVL1312, ADVL1312, UM1CA097452
- Status last verified
- Aug 2023
- First submitted
- 13 Mar 2014
- Last updated
- 26 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02095132
- Acronym / sponsor ID
- NCI-2014-00547
- Conditions
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 Mar 2014 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 24 Mar 2014 (estimated)
- Results
- Posted 5 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of adavosertib (AZD1755 [MK-1775]) administered on days 1 through 5 every 21 days, in combination with oral irinotecan (irinotecan hydrochloride), to children with recurrent or refractory solid tumors.
II. To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
III. To characterize the pharmacokinetics of AZD1755 (MK-1775) in children with refractory cancer.
SECONDARY OBJECTIVES:
- To preliminarily define the antitumor activity of AZD1755 (MK-1775) and irinotecan within the confines of a Phase 1 study.
II. To obtain initial phase 2 efficacy data on the anti-tumor activity of AZD1755 (MK-1775) in combination with irinotecan administered to children with relapsed or refractory neuroblastoma, in children with relapsed or refractory medulloblastoma/CNS PNET (central nervous system primitive neuroectodermal tumor) and in children with relapsed or refractory rhabdomyosarcoma.
III. To investigate checkpoint over-ride by AZD1755 (MK-1775) via the mechanism-based pharmacodynamic (PD) biomarker of decreased cyclin-dependent kinase 1 (CDK1) phosphorylation in correlative and exploratory studies.
IV. To evaluate potential predictive biomarkers of AZD1755 (MK-1775) sensitivity, including v-myc avian myelocytomatosis viral oncogene homolog (MYC), v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), phosphorylated-WEE1 G2 checkpoint kinase (p-Wee1), enhancer of zeste homolog 2 (Drosophila) (EZH2) and gamma-H2A histone family, member gamma-(H2AX) in tumor tissues in correlative and exploratory studies.
OUTLINE: This is a phase I, dose-escalation followed by a phase II study.
Patients receive irinotecan hydrochloride orally (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.
After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (irinotecan hydrochloride, adavosertib) | Experimental | Drug: Adavosertib, Drug: Irinotecan HydrochloridePatients 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. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (42 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdavosertibAlso: AZD-1775, AZD1775, MK-1775, MK1775Given PO | Drug | Treatment (irinotecan hydrochloride, adavosertib) |
| Irinotecan HydrochlorideAlso: Campto, Camptosar, Camptothecin 11, Camptothecin-11Given PO | Drug | Treatment (irinotecan hydrochloride, adavosertib) |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Up to 21 days
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.
Number of Participants With Cycle 1 DLT
Time frame: Up to 21 days
To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, AUC
Time frame: 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
The PK parameters will be summarized by means and standard deviations
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Cmax
Time frame: 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
The PK parameters will be summarized by means and standard deviations
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, HL-Lambda (Half Life)
Time frame: 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
The PK parameters will be summarized by means and standard deviations
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Tmax
Time frame: 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
The PK parameters will be summarized by means and standard deviations
3 secondary outcomes
Number and Percentage of Participants With Best Overall Response With Partial or Complete Response
Time frame: Up to 1 year
Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells
Time frame: Up to 1 day
Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification
Time frame: Assessed at Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristina A Cole principal investigator
COG Phase I Consortium
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Adavosertib and Irinotecan Hydrochloride in people with Central Nervous System Embryonal Tumor With Rhabdoid Features and Central Nervous System Embryonal Tumor, Not Otherwise Specified, run by National Cancer Institute (NCI) at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 42 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Up to 21 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.