Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT03526250

Collaborator

(none)

Enrollment

119

Locations

Arm

84.2

Anticipated Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II Pediatric MATCH trial studies how well palbociclib works in treating patients with Rb positive solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations (mutations) in cell cycle genes that have spread to other places in the body and have come back or do not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Solid Neoplasm Recurrent Childhood Ependymoma Recurrent Ewing Sarcoma Recurrent Glioma Recurrent Hepatoblastoma Recurrent Kidney Wilms Tumor Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Germ Cell Tumor Recurrent Malignant Glioma Recurrent Medulloblastoma Recurrent Neuroblastoma Recurrent Non-Hodgkin Lymphoma Recurrent Osteosarcoma Recurrent Peripheral Primitive Neuroectodermal Tumor Recurrent Rhabdoid Tumor Recurrent Rhabdomyosarcoma Recurrent Soft Tissue Sarcoma Refractory Ependymoma Refractory Ewing Sarcoma Refractory Glioma Refractory Hepatoblastoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Germ Cell Tumor Refractory Malignant Glioma Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Osteosarcoma Refractory Peripheral Primitive Neuroectodermal Tumor Refractory Rhabdoid Tumor Refractory Rhabdomyosarcoma Refractory Soft Tissue Sarcoma	Other: Laboratory Biomarker Analysis Drug: Palbociclib Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with palbociclib with advanced solid tumors (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in cell cycle genes.

SECONDARY OBJECTIVES:

To estimate the progression free survival in pediatric patients treated with palbociclib with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in alterations in cell cycle genes.
To obtain information about the tolerability of palbociclib in children and adolescents with relapsed or refractory cancer.

EXPLORATORY OBJECTIVE:

To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).

OUTLINE:

Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

49 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Palbociclib in Patients With Tumors Harboring Activating Alterations in Cell Cycle Genes

Actual Study Start Date :

Jun 25, 2018

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (palbociclib) Patients receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Correlative studies Drug: Palbociclib Given PO Other Names: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one Ibrance PD 0332991 PD 332991 PD 991 PD-0332991 Other: Pharmacological Study Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (palbociclib)

Patients receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Palbociclib

Given PO

Other Names:

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one

Ibrance

PD 0332991

PD 332991

PD 991

PD-0332991

Other: Pharmacological Study

Correlative studies

Outcome Measures

Primary Outcome Measures

Objective response rate [Up to 5 years]
Defined as a patient who achieves a best response of partial response or complete response on the study. Confidence intervals will be constructed using the Wilson score interval method.

Secondary Outcome Measures

Progression free survival (PFS) [From the initiation of protocol treatment to disease progression or disease recurrence or death from any cause, assessed up to 5 years]
PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
Incidence of adverse events [Up to 5 years]
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Pharmacokinetic (PK) parameters [Up to 5 years]
PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Other Outcome Measures

Changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid [Baseline up to 5 years]
A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621I based on the presence of an actionable mutation as defined in APEC1621SC
In addition to the actionable mutations, positive Rb expression by immunohistochemistry is required for study enrollment
Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment
Patients must have a body surface area >= 0.87 m^2 at enrollment
Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT).
Note: The following do not qualify as measurable disease:
Malignant fluid collections (e.g., ascites, pleural effusions)
Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
Previously radiated lesions that have not demonstrated clear progression post radiation
Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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; for agents not listed, 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 counts [ANC] counts): >= 7 days after the last dose of agent
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 growth factors 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.)
Radiation therapy (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 morrow (BM) radiation
Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have received prior exposure to palbociclib, ribociclib, abemaciclib or any other CDK4/6 inhibitors
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)
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
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; maximum serum creatinine (mg/dL): male 0.6; female 0.6
Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
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
Patients must be able to swallow intact capsules
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 due to risks of fetal and teratogenic adverse events as seen in animal/human studies; 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 for the duration of study treatment; females study participants of child-bearing potential and their partners, should agree to use highly effective forms of contraception for at least 3 weeks after the last dose of palbociclib; male study participants should avoid fathering a child, donating sperm, and should agree to use highly effective forms of contraception for at least 3 months after the last dose of palbociclib
Concomitant medications
Corticosteroids: 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; if used to modify immune adverse events related to prior therapy,

= 14 days must have elapsed since last dose of corticosteroid

Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible
Anti-GVHD agents post-transplant: 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
CYP3A4 agents: Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Banner Children's at Desert	Mesa	Arizona	United States	85202
4	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
5	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
6	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
7	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
8	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
9	Loma Linda University Medical Center	Loma Linda	California	United States	92354
10	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
11	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
12	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
13	Valley Children's Hospital	Madera	California	United States	93636
14	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
15	Kaiser Permanente-Oakland	Oakland	California	United States	94611
16	Children's Hospital of Orange County	Orange	California	United States	92868
17	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
18	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
19	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
20	Children's Hospital Colorado	Aurora	Colorado	United States	80045
21	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
22	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
23	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
24	Children's National Medical Center	Washington	District of Columbia	United States	20010
25	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
26	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
27	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
28	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
29	Nicklaus Children's Hospital	Miami	Florida	United States	33155
30	AdventHealth Orlando	Orlando	Florida	United States	32803
31	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
32	Nemours Children's Hospital	Orlando	Florida	United States	32827
33	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
34	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
35	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
36	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
37	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
38	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
39	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
40	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
41	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
42	Blank Children's Hospital	Des Moines	Iowa	United States	50309
43	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
44	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
45	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
46	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
47	Eastern Maine Medical Center	Bangor	Maine	United States	04401
48	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
49	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
50	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
51	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
52	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
53	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
54	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
55	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
56	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
57	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
58	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
59	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
60	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
61	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
62	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
63	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
64	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
65	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
66	Morristown Medical Center	Morristown	New Jersey	United States	07960
67	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
68	Albany Medical Center	Albany	New York	United States	12208
69	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
70	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
71	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
72	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
73	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
74	University of Rochester	Rochester	New York	United States	14642
75	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
76	Mission Hospital	Asheville	North Carolina	United States	28801
77	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
78	Duke University Medical Center	Durham	North Carolina	United States	27710
79	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
80	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
81	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
82	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
83	Dayton Children's Hospital	Dayton	Ohio	United States	45404
84	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
85	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
86	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
87	Oregon Health and Science University	Portland	Oregon	United States	97239
88	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
89	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
90	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
91	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
92	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
93	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
94	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
95	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
96	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
97	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
98	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
99	Medical City Dallas Hospital	Dallas	Texas	United States	75230
100	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
101	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
102	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
103	M D Anderson Cancer Center	Houston	Texas	United States	77030
104	Covenant Children's Hospital	Lubbock	Texas	United States	79410
105	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
106	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
107	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
108	Scott and White Memorial Hospital	Temple	Texas	United States	76508
109	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
110	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
111	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
112	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
113	Seattle Children's Hospital	Seattle	Washington	United States	98105
114	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
115	Madigan Army Medical Center	Tacoma	Washington	United States	98431
116	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
117	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
118	San Jorge Children's Hospital	San Juan		Puerto Rico	00912
119	University Pediatric Hospital	San Juan		Puerto Rico	00926