Cyclophosphamide for CNS Neoplasm

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
St. Jude Children's Research Hospital, Memphis, TN
CNS Neoplasm+16 More
Cyclophosphamide - Drug
Eligibility
< 65
All Sexes
What conditions do you have?
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Study Summary

Evaluation of LY2606368 Therapy in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group 4 or SHH Medulloblastoma Brain Tumors

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Eligible Conditions

  • CNS Neoplasm
  • Medulloblastoma, Non-WNT/Non-SHH, Group 3
  • Medulloblastoma, Non-WNT/Non-SHH, Group 4
  • CNS Cancer
  • Tumors of the Central Nervous System
  • Pediatric Brain Tumors
  • Medulloblastoma Recurrent
  • Medulloblastoma
  • Medulloblastoma, Non-WNT/Non-SHH
  • Recurrent Brain Tumors
  • Cancer Brain
  • Refractory Brain Tumors
  • Neoplasms, Brain

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

This trial is evaluating whether Cyclophosphamide will improve 4 primary outcomes and 10 secondary outcomes in patients with CNS Neoplasm. Measurement will happen over the course of prexasertib and cyclophosphamide treatment course 1, day 1.

Month 1
Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
Year 1
Duration of objective response by stratum
Rate of objective response (complete or partial response) by stratum
Year 2
To determine the safety and tolerability of combination treatment with prexasertib and cyclophosphamide or gemcitabine.
Year 3
Progression-free survival for patients treated with prexasertib and cyclophosphamide or gemcitabine
Day 2
To characterize the area under the concentration-time curve (AUC0-∞) of prexasertib in combination with cyclophosphamide or gemcitabine.
To characterize the systemic clearance (CL) of prexasertib in combination with cyclophosphamide or gemcitabine.
Day 1
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine triphosphate (only at St. Jude Children's Research Hospital).
To characterize the systemic clearance (CL) of gemcitabine.
Day 1
To characterize the area under the concentration-time curve (AUC0-24h) of 4-hydroxy-cyclophosphamide.
To characterize the area under the concentration-time curve (AUC0-24h) of carboxyethylphosphoramide mustard.
To characterize the area under the concentration-time curve (AUC0-24h) of cyclophosphamide.
To characterize the systemic clearance (CL) of cyclophosphamide.
Day 1
To characterize the area under the concentration-time curve (AUC0-4h) of gemcitabine.

Trial Safety

Safety Progress

1 of 3

Trial Design

2 Treatment Groups

A: prexasertib + cyclophosphamide
1 of 2
B: prexasertib + gemcitabine
1 of 2
Experimental Treatment

This trial requires 21 total participants across 2 different treatment groups

This trial involves 2 different treatments. Cyclophosphamide is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

A: prexasertib + cyclophosphamideStratum A: Participants receive combination treatment with cyclophosphamide given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, cyclophosphamide may be given on day 16 and prexasertib may be given on day 17.
B: prexasertib + gemcitabineStratum B: Participants receive combination treatment with gemcitabine given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, gemcitabine may be given on day 16 and prexasertib may be given on day 17.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cyclophosphamide
FDA approved
Prexasertib
Not yet FDA approved
Gemcitabine
FDA approved
Filgrastim
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to 3 years from diagnosis
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly up to 3 years from diagnosis for reporting.

Closest Location

St. Jude Children's Research Hospital - Memphis, TN

Eligibility Criteria

This trial is for patients born any sex aged 65 and younger. You must have received 1 prior treatment for CNS Neoplasm or one of the other 16 conditions listed above. There are 4 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Inclusion Criteria: Screening Phase
Participants with recurrent, refractory, or progressive medulloblastoma.
Age ≥ 1 year and < 25 years at the time of screening.
Participants and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.

Patient Q&A Section

How many people get medulloblastoma a year in the United States?

"We found an annual incidence at age 0 to 4 years of 0.1/1000 population. The incidence increased in older children and young adults. The median age at diagnosis was 7.2 years. Survival in patients younger than 1 year was 63%, 50%, 67%, and 47% after 10, 20, and 30 years, respectively. Survival was 50%, 52%, and 69% after 10, 20, and 30 years, respectively, in patients older than 4 years of age. Survival was not adversely affected by advancing age. The authors concluded that the incidence of medulloblastoma has not increased during the last four decades and are concerned that this may be because there has not been an appreciable increase in childhood or childhood cancer rates." - Anonymous Online Contributor

Unverified Answer

What is medulloblastoma?

"Medulloblastoma is the most common primary pediatric tumour diagnosed in America. Although metastatic disease is not uncommon, local disease persists for the majority of patients in the first two years of life. Survival analysis suggests that age at diagnosis and tumor grade are important factors." - Anonymous Online Contributor

Unverified Answer

What are common treatments for medulloblastoma?

"The standard of treatment in medulloblastoma is chemotherapy with cranioplasty for tumor control and craniofacial reconstruction. No evidence-based clinical trials have shown benefit for other treatments. New therapies and chemotherapy regimens are needed for medulloblastoma." - Anonymous Online Contributor

Unverified Answer

What are the signs of medulloblastoma?

"The symptoms of medulloblastoma, which are common and non-specific, can result in the diagnostic delay. Patients may exhibit headache, nausea, or vomiting. The most common sign of medulloblastoma is strabismus." - Anonymous Online Contributor

Unverified Answer

Can medulloblastoma be cured?

"The current knowledge of medulloblastoma comes from a small, small number of patients, many of whom received aggressive chemotherapy for medulloblastoma of the central nervous system. Most of these patients have a disease-free interval of 5 years or more, but others may have a shorter disease-free interval. Medulloblastoma that is cured does not always have long-lasting effects, and more research is needed." - Anonymous Online Contributor

Unverified Answer

What causes medulloblastoma?

"Most medulloblastomas appear to result from chromosomal instability in the neural precursor cells of the cerebellum. For most children, most medulloblastomas that are found occur as disseminated disease. There is no compelling evidence that hereditary factors play a role in the causation of medulloblastoma. However, there is a possible hereditary association with tumors of the pons and cerebellum in children." - Anonymous Online Contributor

Unverified Answer

What is the survival rate for medulloblastoma?

"The survival rate is 91.2% after surgery, 81.6% after chemotherapy, and 76.2% after radiotherapy for medulloblastoma. Data from a recent study provide prognostic information for patients and patients' families. There is still little information available on the best treatments, including surgery or radiotherapy for the most children who have this disease, and the optimal chemotherapy regimen for the most children with medulloblastoma. The most important prognostic factors for survival are the extent of surgery, the child's age, the child's performance score, and the child's overall health." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating medulloblastoma?

"There are now a number of well-established and successful treatment paths for patients with medulloblastoma, which are based on a wide range of biological and clinical factors. As our knowledge of cancer biology increases, the number and variety of therapeutic options are likely to increase in the future." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving cyclophosphamide?

"Cyclophosphamide has been used in a variety of contexts in addition to [multiple myeloma](https://www.withpower.com/clinical-trials/multiple-myeloma) and medulloblastoma, including rheumatoid arthritis, lupus erythematosus and some other types of cancer. While several of these studies were large in size, our review revealed a paucity of trials addressing myeloma in general. When such clinical trials have been conducted for medulloblastoma, they commonly target younger patients and employ newer therapies, but the experience of pediatricians with myeloma patients is probably not well established." - Anonymous Online Contributor

Unverified Answer

What does cyclophosphamide usually treat?

"The [Molecule Activity Score (MAS)] is a method of estimating the drug's effectiveness that can identify cyclophosphamide molecules that are specifically harmful to cancer cells. Results from a recent clinical trial do not support the use of cyclophosphamide. We found that [Mas score of 1.6±0.2] is a cutoff point for identifying highly toxic molecules, but we did not find any molecules that had a lower mas. [Mas score of 1.9±0.3] was the highest value predicted, indicating that cyclophosphamide can kill some patients." - Anonymous Online Contributor

Unverified Answer

Does cyclophosphamide improve quality of life for those with medulloblastoma?

"Cyclophosphamide significantly improved global functioning and QOL in children with medulloblastoma. With our sample size, the magnitude of this effect is not significant. The improvement appears to be related to better functioning and not better QOL. Although patients may be better able to cope with their illness, with chemotherapy, the magnitude of this intervention is not significant and would not necessarily improve QOL. Overall, the results suggest that cyclophosphamide and radiation therapy should be considered a primary treatment in patients with medulloblastoma." - Anonymous Online Contributor

Unverified Answer

What are the chances of developing medulloblastoma?

"Children who develop nephrotic syndrome during or after exposure of the fetus to radiation have a 6-fold increase in the risk of medulloblastoma, which persists for at least 20 years. Medulloblastomas have been reported in children with in utero radiation exposure. To minimize the risk of developing medulloblastoma, physicians should counsel parents for their potential future occurrence of nephrotic syndrome during and after exposure of the fetus to ionizing radiation or other mutagens." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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