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Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy


N/A
5 Years
40 Years
Not Enrolling
Both
Osteosarcoma

Thank you

Trial Information

Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy


The Study Drugs:

The standard treatment combination used to treat patients with osteosarcoma is doxorubicin,
cisplatin, and methotrexate with or without ifosfamide. When this treatment combination is
given in the hospital, it can require around 18-22 hospital stays. Somewhat recently,
chemotherapy for osteosarcoma has become possible to give in the outpatient clinic.
Researchers want to learn if giving 4 certain drugs (the combination of doxorubicin,
cisplatin, and methotrexate with or without ifosfamide) in the outpatient setting to
eligible patients will help to decrease the number of hospital stays.

During this study, all study participants whose tumor(s) can be taken out with surgery will
be offered routine surgery to remove the tumor(s). After surgery, if the doctor believes
the tumor(s) have responded well enough, the standard treatment combination is again
doxorubicin, cisplatin, and methotrexate. If the tumor(s) have not responded well enough,
however, the standard treatment combination is methotrexate and ifosfamide.

In this study, participants are considered at "higher risk" for the tumor(s) spreading to
the lungs in the following cases: if the participant's tumor(s) are large at the time of
joining this study, if the cancer has spread to other organs, and/or if standard
chemotherapy in this study has not killed enough tumor cells.

The following drugs are used in this study:

- Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells
to die.

- Cisplatin has an atom at its center that contains a type of metal called platinum. The
platinum is supposed to poison the cancer cells.

- Methotrexate is designed to disrupt cells (including cancer cells) from making and
repairing DNA and "copying" themselves.

- Ifosfamide is designed to stop the growth of cancer cells, which may cause the cells to
die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
groups based on the likelihood that the surgery will be able to control the disease in the
arm or leg that has the bone tumor(s).

Group 1 includes participants who are considered to have a "standard" chance that surgery
will be able to control the disease in the arm or leg, participants who will have an
amputation, or participants with cancer in areas other than in an arm or leg at the time of
diagnosis.

Group 2 includes participants who are considered to have a "higher" chance that the tumor(s)
will be left behind after having surgery that the doctor considers as "incomplete" to
control the disease.

Central Venous Line:

For drugs to be given by vein, your study doctor will likely recommend that you have a
central venous line (CVL) placed. A central venous line is a sterile flexible tube that
will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form for this procedure.

Pre-Surgery Chemotherapy for Group 1:

Before surgery, Group 1 participants will receive doxorubicin, cisplatin, and methotrexate
followed by leucovorin. Leucovorin is given to help prevent and/or treat the side effects
that methotrexate may cause. Dexrazoxane is used to decrease the risk of side effects to
the heart that doxorubicin may cause. These drugs will be given in an outpatient clinic
(without requiring hospitalization), if possible.

Doxorubicin will be given by vein over 15 minutes, after dexrazoxane by vein over 15
minutes, on Day 1 of Weeks 1 and 6.

Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2 of
Weeks 1 and 6.

Methotrexate will be given by vein, over 4 hours, on Day 1 of Weeks 4, 5, 9, and 10. If you
have difficulty recovering from the effects of the methotrexate therapy, you may only
receive methotrexate twice before surgery, instead of 4 times.

Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose
and then by mouth every 6 hours after that, until the study doctor believes that the
methotrexate level in the blood is low. The methotrexate level in the blood will be checked
using a blood test (less than 2 teaspoons each time). This test will be performed once a
day after each methotrexate infusion, until the methotrexate blood level is low and it is
considered safe to stop the leucovorin.

Pre-Surgery Chemotherapy for Group 2:

Before surgery, Group 2 participants will receive dexrazoxane, doxorubicin, and cisplatin.

On Day 1 of Weeks 1, 4, and 7, dexrazoxane will be given by vein over 15 minutes, followed
by doxorubicin given by vein over 15 minutes and then cisplatin through an artery over 4
hours. Infusion through an artery requires a hospital stay of 2-4 days.

Surgery:

For all eligible study participants, the surgery to remove the tumor(s) will be performed on
either Week 11 or 12. The surgery will be explained to you in detail, and you will be asked
to sign a separate consent form for it that will describe its risks.

Before surgery, you will have routine visits with the surgeon. You will have several
routine scans performed to help plan the surgery.

Chemotherapy Regimens after Surgery:

After the surgery (on or around Week 14), you will receive additional "post-surgery"
chemotherapy.

After surgery, if you were originally in Group 1, and if the doctor believes the tumor(s)
have responded well enough (specifically, if 90% or more of the tumor cells are dead when
checked under the microscope), you will receive additional chemotherapy that is similar to
what you received before surgery. This is described below as Regimen A. If the doctor does
not believe the tumor(s) have responded well enough (if less than 90% of the tumor cells are
dead when checked under the microscope), however, you will be assigned to Regimen B.

All participants who started in Group 2 will be assigned to Regimen B.

Radiation and Chemotherapy for Patients Ineligible for Routine Surgery:

A small number of participants on this study may need to have radiation therapy to help
control the disease, as part of their routine care. This would only be done if the tumor(s)
cannot be completely taken out with surgery, or if amputation is necessary but refused by
the participant. If needed, and depending on where the tumor(s) are located, your doctor
may decide that radiation is needed. All participants needing radiation or having surgery
that the doctor considers as "incomplete" to control the disease are considered "higher
risk" and will receive Regimen B therapy during and after radiation. (Radiation will
usually begin during Weeks 12-14, but it could be anytime during ifosfamide therapy.) The
radiation therapy will be explained to you in detail, and you will be asked to sign a
separate consent form for it that will describe its risks.

Post-Surgery Chemotherapy for Regimen A:

Regimen A includes the following treatments:

- Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29,
and 30.

- Doxorubicin will be given on Day 1 of Weeks 16, 21, and 26.

- Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2
of Weeks 16, 21, and 26.

- Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate
dose and then by mouth every 6 hours after that, until the study doctor believes that
the methotrexate level in the blood is low. The methotrexate level in the blood will
be checked using a blood test (less than 2 teaspoons each time). This test will be
performed once a day after each methotrexate infusion, until the methotrexate blood
level is low and it is considered safe to stop the leucovorin.

Post-Surgery Chemotherapy for Regimen B:

Regimen B includes the following treatments:

- Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32,
33, 38, and 39.

- Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate
dose and then by mouth every 6 hours after that, until the study doctor believes that
the methotrexate level in the blood is low. The methotrexate level in the blood will
be checked using a blood test (less than 2 teaspoons each time). This test will be
performed once a day after each methotrexate infusion, until the methotrexate blood
level is low and it is considered safe to stop the leucovorin.

- Ifosfamide will be given by vein, continuously over 5 days each time, on Weeks 16, 22,
28, and 34.

- Mesna will be given by vein, continuously over 6 days each time, on Weeks 16, 22, 28,
and 34. Mesna is used to decrease the risk of bleeding in the bladder and kidneys
while ifosfamide is taken.

Study Tests:

After Week 5 of treatment, and then again before surgery, you will have the following tests
performed:

- Your medical history will be reviewed.

- You will have a physical exam.

- Blood (about 2-3 teaspoons each time) will be collected for routine tests and tests of
your kidney and liver function. The routine blood tests may be repeated more often
during the weeks you are receiving any of the study drugs.

If you are receiving cisplatin, you may have a hearing test performed before each dose of
this drug.

You will have an ECHO performed before your fourth dose of doxorubicin on Week 14, and
possibly more often if necessary.

Questionnaires:

You will be asked to complete 5 brief questionnaires on 5 different days during this study.
The questionnaires ask about the health-related quality of your life, and include questions
about how you have felt, physically and emotionally, during cancer treatment. The
questionnaires also ask how you and your family have adapted to your having cancer
treatments, and what effects the medicines may have had on whether you have felt healthy or
sick.

These questionnaires will be completed at Week 1, at about Week 7 (before surgery or
radiation), sometime during Weeks 20-22, at the end-of-treatment visit (either the
end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit), and 1
year after your first diagnosis of cancer. It should take you about 15-20 minutes to fill
out the questionnaires each time.

External Care:

If the study doctor allows and you agree, some of the blood tests in this study may be
performed outside of M. D. Anderson. The study doctor will discuss this option with you, if
applicable.

Length of Study Participation:

If the disease gets worse or intolerable side effects occur, you will be taken off study.

End-of-Regimen-A Visit, End-of-Regimen-B Visit, or End-of-Treatment Visit:

If you complete Regimen A or B as planned or you leave the study early for any reason, the
following procedures will be performed:

- You will have a physical exam.

- Urine and blood (about 2-3 teaspoons) will be drawn for routine tests and tests of your
kidney and liver function.

- You will have an ECHO, x-rays of the disease area and the chest, CT scans of the chest,
and a bone scan.

- You will also have whole-body scans and a hearing test.

Follow-Up Visits:

After the end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit,
you will be asked to return for follow-up visits. At these visits, the following procedures
will be performed:

- CT scans of the chest will be performed every 3 months for the first year after your
chemotherapy ends, every 4 months for the 2nd year, every 6 months for the 3rd year,
and once a year for the next 2 years.

- You will have a bone scan every year for 5 years.

This is an investigational study. All of the drugs used in this study are commercially
available and commonly used in osteosarcoma. This study is designed to look at the drugs'
use in the outpatient setting, which is considered research.

Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Newly diagnosed high-grade osteosarcoma. Patients with unresectable or metastatic
disease ARE eligible.

2. Age 5-40 years old on date of diagnostic biopsy.

3. Adequate organ function: creatinine 1.6 or lower, bilirubin <2, Hemoglobin 8 gm/dL or
greater, Absolute neutrophil count (ANC) 1000 or more, platelets 100,000 or more.
Cardiac ejection fraction (EF) 50% or better, hearing threshold 40 dB at 4000 Hz or
better.

4. Signed informed consent.

5. Negative pregnancy test in females of child bearing potential, and if sexually
active, willingness to use effective contraception during chemotherapy.

Exclusion Criteria:

1. Diagnosis other than osteosarcoma.

2. Pregnant or lactating females, or unwilling to use effective contraception during
chemotherapy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment Success (6 or fewer hospitalizations during front-line chemotherapy)

Outcome Time Frame:

Baseline to 5 Years

Safety Issue:

Yes

Principal Investigator

Peter M. Anderson, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2007-0404

NCT ID:

NCT00673179

Start Date:

May 2008

Completion Date:

November 2010

Related Keywords:

  • Osteosarcoma
  • Doxorubicin
  • AD
  • Hydroxydaunomycin hydrochloride
  • Cisplatin
  • Paraplatin®
  • Methotrexate
  • Ifosfamide
  • Osteosarcoma
  • Sargramostim
  • Leukine™
  • Leucovorin
  • Gemcitabine
  • Gemzar
  • Gemcitabine Hydrochloride
  • GM-CSF
  • Questionnaire
  • Survey
  • Osteosarcoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030