Clinical Trial

PNOC027: A pilot trial of real time drug screening and genomic testing to determine an individualized treatment plan in children and young adults with relapsed medulloblastoma

This study will enroll children and young adults (age 12 months to 39 years of age) with relapsed medulloblastoma.

The study will use a new treatment approach based on the molecular characteristics of each participant’s tumor. The study will test the feasibility of performing real-time drug screening on tissue taken during surgery, and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with medulloblastoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.

To determine the feasibility of using the results of real-time in vitro drug screening, whole exome sequencing, and RNA sequencing of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma.

Subjects must have baseline evaluations performed prior to start of protocol treatment and must meet all inclusion and none of the exclusion criteria. In addition, the patient and/or their legal guardian must be thoroughly informed about all aspects of the study, including the study visit schedule, required evaluations and all regulatory requirements. The written informed consent must be obtained from the patient or their legal guardian prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.

Inclusion Criteria:

  • Participants must have recurrent medulloblastoma.
  • Participants must have surgically accessible disease.
  • Prior Therapy:
    • The participant must have recurrent medulloblastoma following at least one prior therapy for initial diagnosis or previous recurrence– surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy – prior to study registration.
    • Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
      • Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to study registration (6 weeks prior if nitrosourea).
      • Biologic agent: Participant must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent no less than 7 days prior to study registration.
        • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
        • For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
      • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration.  Such participants should be discussed with the study chair prior to registration. For bevacizumab, participants must have received last dose > 32 days prior to study registration.
      • Bone Marrow Transplant: Participant must be:
        • ≥ 6 months since allogeneic bone marrow transplant prior to registration
        • ≥ 3 months since autologous bone marrow/stem cell prior to registration
      • Participant must be a candidate for surgical resection or biopsy. Minimum tissue requirements for study are defined in Section 9.1.
      • Radiation: Participants must have:
        • Had their last fraction of local irradiation to primary tumor ≥ 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
        • Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12 weeks prior to registration
        • At least 14 days after local palliative radiation (small-port)
      • Age ≥12 months to ≤ 39 years of age
      • Karnofsky ≥50 for participants > 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age (See Appendix A). Participants 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.
      • Corticosteroids: Subjects who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.
      • Organ Function Requirements (within 7 days prior to study registration)
        • Adequate Bone Marrow Function Defined as:
          • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
          • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
        • Adequate Renal Function Defined as:
          • Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or
          • A serum creatinine based on age/gender as follows:
Age Maximum Serum
Creatinine (mg/dL)
  Male Female
1 to < 2 years 0.6 0.6
2 to < 6 years 0.8 0.8
6 to < 10 years 1 1
10 to < 13 years 1.2 1.2
13 to < 16 years 1.5 1.4
≥ 16 years 1.7 1.4

The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.1

  • Adequate Liver Function Defined as:
    • Bilirubin (sum of conjugated + unconjugated) ≤1.5 x upper limit of normal (ULN) for age.
    • SGPT (ALT) ≤110 U/L.
    • Serum albumin ≥ 2 g/dL.
  • The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Adequate neurologic function defined as:
    • Participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. See Appendix B for a list of recommended non-enzyme inducing anticonvulsants
  • A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion Criteria

  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants who are receiving any other investigational agents.
  • Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
  • Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
  • Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.

Support is provided by the St. Baldrick’s Foundation

This study will enroll children and young adults (age 12 months to 39 years of age) with relapsed medulloblastoma.

The study will use a new treatment approach based on the molecular characteristics of each participant’s tumor. The study will test the feasibility of performing real-time drug screening on tissue taken during surgery, and of having a specialized tumor board assign a treatment plan based on the results of this screening and genomic sequencing. The aim of this trial is to allow every child and young adult with medulloblastoma to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.

To determine the feasibility of using the results of real-time in vitro drug screening, whole exome sequencing, and RNA sequencing of participant-derived specimens to guide treatment recommendations by a specialized tumor board, in a clinically-actionable timeframe, for children and young adults with recurrent medulloblastoma.

Subjects must have baseline evaluations performed prior to start of protocol treatment and must meet all inclusion and none of the exclusion criteria. In addition, the patient and/or their legal guardian must be thoroughly informed about all aspects of the study, including the study visit schedule, required evaluations and all regulatory requirements. The written informed consent must be obtained from the patient or their legal guardian prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified.

Inclusion Criteria:

  • Participants must have recurrent medulloblastoma.
  • Participants must have surgically accessible disease.
  • Prior Therapy:
    • The participant must have recurrent medulloblastoma following at least one prior therapy for initial diagnosis or previous recurrence– surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy – prior to study registration.
    • Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
      • Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to study registration (6 weeks prior if nitrosourea).
      • Biologic agent: Participant must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent no less than 7 days prior to study registration.
        • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
        • For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
      • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration.  Such participants should be discussed with the study chair prior to registration. For bevacizumab, participants must have received last dose > 32 days prior to study registration.
      • Bone Marrow Transplant: Participant must be:
        • ≥ 6 months since allogeneic bone marrow transplant prior to registration
        • ≥ 3 months since autologous bone marrow/stem cell prior to registration
      • Participant must be a candidate for surgical resection or biopsy. Minimum tissue requirements for study are defined in Section 9.1.
      • Radiation: Participants must have:
        • Had their last fraction of local irradiation to primary tumor ≥ 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
        • Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12 weeks prior to registration
        • At least 14 days after local palliative radiation (small-port)
      • Age ≥12 months to ≤ 39 years of age
      • Karnofsky ≥50 for participants > 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age (See Appendix A). Participants 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.
      • Corticosteroids: Subjects who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration.
      • Organ Function Requirements (within 7 days prior to study registration)
        • Adequate Bone Marrow Function Defined as:
          • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
          • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
        • Adequate Renal Function Defined as:
          • Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or
          • A serum creatinine based on age/gender as follows:
Age Maximum Serum
Creatinine (mg/dL)
  Male Female
1 to < 2 years 0.6 0.6
2 to < 6 years 0.8 0.8
6 to < 10 years 1 1
10 to < 13 years 1.2 1.2
13 to < 16 years 1.5 1.4
≥ 16 years 1.7 1.4

The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.1

  • Adequate Liver Function Defined as:
    • Bilirubin (sum of conjugated + unconjugated) ≤1.5 x upper limit of normal (ULN) for age.
    • SGPT (ALT) ≤110 U/L.
    • Serum albumin ≥ 2 g/dL.
  • The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Adequate neurologic function defined as:
    • Participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug. See Appendix B for a list of recommended non-enzyme inducing anticonvulsants
  • A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion Criteria

  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants who are receiving any other investigational agents.
  • Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
  • Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
  • Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.

Support is provided by the St. Baldrick’s Foundation

Sites Offering This Trial

How to Enroll

If you believe your child or patient is eligible for this trial, contact the closest participating site or email us for more information.