Inclusion:

          1. Histologically confirmed relapsed or refractory solid tumor as follows:

               -  For dose escalation and dose determination parts: Histologically confirmed
                  relapsed or refractory solid tumor (including CNS tumors but not lymphomas).
                  Patients with Diffuse Intrinsic Pontine Glioma do not require histological only
                  radiographic confirmed relapse to enroll.

               -  For dose expansion and tumor specific cohorts: Histologically confirmed relapsed
                  or refractory solid tumor including but not limited to EWS, rhabdoid tumor,
                  rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse
                  Intrinsic Pontine Glioma do not require histological only radiographic confirmed
                  relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.

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

          3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative
             Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.

          4. Adequate bone marrow function.

               -  Absolute neutrophil count ≥1000/mm3;

               -  Platelet count ≥100,000/mm3 (transfusion independent);

               -  Hemoglobin ≥8.5 g/dL (transfusion allowed).

          5. Adequate renal function: Serum creatinine level based on age/gender must within
             protocol specified limits.

          6. 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.

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

          8. 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.

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

         10. Evidence of a personally signed and dated informed consent document indicating that
             the patient or a legally acceptable representative/parent(s)/legal guardian of 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
             applicable.

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

        Exclusion:

          1. For palbociclib with IRN and TMZ combination, 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. For patients enrolling in the palbociclib with TOPO
             and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on
             treatment with a TOPO-containing regimen that includes CTX. Patients who have received
             the combination of TOPO and CTX and did not progress while on these medications are
             eligible.

          2. Prior intolerability to IRN and/or TMZ, for palbociclib with IRN and TMZ combination
             and prior intolerability to TOPO and/or CTX for palbociclib with TOPO and CTX
             combination.

          3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are
             receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors
             within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN
             and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12
             days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See
             Section 5.7.1 for list of products.)

          4. Prior growth factors (including filgrastim) 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
             nitrosoureas.

          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 (see Appendix 9).

          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.