This study will evaluate palbociclib in combination with chemotherapy (temozolomide and irinotecan) in children, adolescents and young adults with recurrent or refractory solid tumors. The main purpose of this study is to evaluate the safety of palbociclib in combination with chemotherapy in order to estimate the maximum tolerated dose. Pharmacokinetics and efficacy of palbociclib in combination with chemotherapy will be evaluated.



Eligible Ages
Between 2 Years and 20 Years
Eligible Genders
Accepts Healthy Volunteers



1. For dose escalation part: Histologically confirmed solid tumor (including CNS tumors
but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require
histological only radiographic confirmed relapse to enroll

2. For dose expansion cohort: Histologically confirmed solid tumor including but not
limited to Ewing sarcoma, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and
medulloblastoma.Patients with Diffuse Intrinsic Pontine Glioma do not require
histological only radiographic confirmed relapse to enroll

3. For tumor-specific cohorts: Histologically confirmed solid tumor including but not
limited to rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma.
Patients with Diffuse Intrinsic Pontine Glioma do not require histological only
radiographic confirmed relapse to enroll. Ewing sarcoma is not eligible for
tumor-specific cohorts.

4. Age ≥2 and <21 years at the time of study entry.

5. Lansky performance status ≥50% for patients ≤12 years of age, or Eastern Cooperative
Oncology Group (ECOG) 0, 1 or 2 for patients >12 years of age.

6. Adequate bone marrow function: Absolute neutrophil count ≥1000/mm3; Platelet count
≥100,000/mm3 (transfusion independent); Hemoglobin ≥8.5 g/dL (transfusion allowed);

7. Adequate renal function (serum creatinine level based on age/gender must be less than
or equal to the maximum upper limits specified in protocol)

8. Adequate liver function, including:Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if
attributable to disease involvement of the liver; Total bilirubin ≤1.5 × ULN for age.

9. Measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS
disease or INRC for neuroblastoma.

10. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute
toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy,
differentiation therapy or biologic therapy, with the exception of alopecia.

11. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and
at the baseline visit.

12. Evidence of a personally signed and dated informed consent document indicating that
the patient or a legally acceptable representative/parent(s)/legal guardian, for
minors, has been informed of all pertinent aspects of the study. Minor study patients
also must provide age appropriate assent according to the local guidelines, where

13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other procedures.


1. Prior treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing regimen that includes TMZ. Patients who have received the combination
of IRN and TMZ and did not progress while on these medications are eligible.

2. Prior intolerability to IRN and/or TMZ.

3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers or strong uridine
diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1
Day 1 (C1D1).

4. Prior growth factors within 7 days before study entry or peg-filgrastim within 14 days
before study entry.

5. Radiation therapy within 14 days before study entry.

6. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for

7. Previous high dose chemotherapy requiring stem cell rescue within 90 days or
persistent AE >Grade 1.

8. Prior irradiation to >50% of the bone marrow.

9. Participation in other studies involving investigational drug(s) within 2 weeks or 5
half lives, whichever is longer, prior to study entry.

10. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line
placement are not considered major surgeries.

11. Known or suspected hypersensitivity to palbociclib, IRN and/or TMZ.

12. Patients with known symptomatic brain tumors or brain metastases and require steroids,
unless they have been on a stable or on a decreasing steroid dose for >14 days.

13. Patients with previously diagnosed brain metastases are eligible if they have
completed their prior treatment and have recovered from the acute effects of radiation
therapy or surgery prior to study entry for these metastases for at least 14 days post
radiation and 4 weeks post-surgery and are neurologically stable.

14. Hereditary bone marrow failure disorder.

15. QTc >470 msec.

16. History of clinically significant or uncontrolled cardiac disease, including: history
of or active congestive heart failure; if patient had congestive heart failure resolve
and >1 year from resolution, patient will be considered eligible; clinically
significant ventricular arrhythmia (such as ventricular tachycardia, ventricular
fibrillation or Torsades de Pointes); diagnosed or suspected congenital or acquired
prolonged QT syndrome; need for medications known to prolong the QT interval;
uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT
interval; left ventricular ejection fraction <50% or shortening fraction <28%.

17. Recent or ongoing clinically significant gastrointestinal disorder that may interfere
with absorption of orally administered drugs (eg, gastrectomy).

18. Evidence of serious active or uncontrolled bacterial, fungal or viral infection or
known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
infection or acquired immunodeficiency syndrome-related illness.

19. Other severe acute or chronic medical or laboratory test abnormality that may increase
the risk associated with study participation or investigational product administration
or may interfere with the interpretation of study results, and in the judgment of the
Investigator, would make the patient inappropriate for entry into this study.

20. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.

21. Fertile male patients and female patients of childbearing potential who are unwilling
or unable to use a highly effective method of contraception as outlined in this
protocol for the duration of the study and for at least 90 after the last dose of
investigational product.

Study Design

Phase 1
Study Type
Intervention Model
Sequential Assignment
Intervention Model Description
The study will be conducted of 3 parts: a dose escalation part (following a rolling 6 design), a dose expansion part, and if applicable, tumor-specific expansion part.
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Single Arm
Palbociclib in combination with temozolomide and irinotecan
  • Drug: Palbociclib
    Administered (oral) at 55 mg/m2, 75 mg/m2, or 40 mg/m2 on days 1-14 of a 21-day cycle
    Other names:
    • Ibrance
  • Drug: Temozolomide
    Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
  • Drug: Irinotecan
    Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010

More Details


Study Contact

Pfizer CT.gov Call Center


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.