OsteosarcomaNCT00673179
Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy
A study testing Doxorubicin, Cisplatin and Methotrexate in people with Osteosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. Read more about this study
- Who is it for?
- Ages 5 to 40 years
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- Doxorubicin, Cisplatin and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Nov 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Newly diagnosed high-grade osteosarcoma. Patients with unresectable or metastatic disease ARE eligible.
- Age 5-40 years old on date of diagnostic biopsy.
- 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.
- Signed informed consent.
- Negative pregnancy test in females of child bearing potential, and if sexually active, willingness to use effective contraception during chemotherapy.
Who cannot join
- Diagnosis other than osteosarcoma.
- Pregnant or lactating females, or unwilling to use effective contraception during chemotherapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy
The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. The drugs and schedules will vary depending on the status of the cancer and its level of risk for spreading, but they will include combinations of doxorubicin (non-liposomal), cisplatin, methotrexate, and ifosfamide, as described below.
Read the detailed description
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.
- Conditions
- Osteosarcoma
- Being tested
- Doxorubicin, Cisplatin, Methotrexate, Leucovorin, Dexrazoxane
- Keywords
- Doxorubicin, AD, Hydroxydaunomycin hydrochloride, Cisplatin, Paraplatin®, Methotrexate, Ifosfamide, Osteosarcoma, Sargramostim, Leukine™, Leucovorin, Gemcitabine, Gemzar, Gemcitabine Hydrochloride, GM-CSF, Questionnaire, Survey
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called AD, Hydroxydaunomycin hydrochloride
Pre-Surgery, Regimen 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Regimen 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2.
CisplatinDrug
Also called Paraplatin®
Pre-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Regimen 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion.
MethotrexateDrug
Pre-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Regimen 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours.
LeucovorinDrug
Pre- and Post-Surgery, Regimen 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Regimen 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours.
DexrazoxaneDrug
Also called Zinecard
Dose 900 mg/m^2 IV Push with doxorubicin. Pre-Surgery, Regimen 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7.
IfosfamideDrug
Also called Ifex
Post-Surgery, Regimen 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2. Dose 2.8 grams m^2/day.
QuestionnaireBehavioural
Also called Survey
Questionnaires to be completed on 5 different days during the study.
GemcitabineDrug
Also called Gemzar, Gemcitabine Hydrochloride
IV over 1 hour, every other week.
SargramostimDrug
Also called GM-CSF, Leukine™
Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine.
SurgeryProcedure or surgery
Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.
MesnaDrug
Also called Mesnex
IV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2/day.
| Study group | Role | What they receive |
|---|---|---|
| Outpatient Chemotherapy | Experimental | Pre-Surgery, Regimen 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m^2/day for 2 days, Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen 1: Methotrexate 12 gm/m^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m^2 twice daily, Leucovorin Rescue. Receives: Drug: Doxorubicin; Drug: Cisplatin; Drug: Methotrexate; Drug: Leucovorin; Behavioral: Questionnaire; Procedure: Surgery |
| Additional Risk-Adapted Outpatient Chemotherapy | Experimental | Pre-Surgery, Regimen 2: Dexrazoxane 900 mg/m^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m^2 (intra-arterial); Surgery; Post-Surgery, Regimen 2: Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m^2/day and Mesna 2.8 gm/m^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg). Receives: Drug: Doxorubicin; Drug: Cisplatin; Drug: Methotrexate; Drug: Leucovorin; Drug: Dexrazoxane; Drug: Ifosfamide; Behavioral: Questionnaire; Drug: Gemcitabine; Drug: Sargramostim; Procedure: Surgery; Drug: Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Success (6 or Fewer Hospitalizations During Front-line Chemotherapy)
Treatment success defined as a patient having 6 or fewer hospitalizations during front-line chemotherapy.
Measured: Baseline to 5 Years
Secondary outcomes (1)
Quality of Life (Ped QL) Assessment
Measured: Peds QL measures at week 0 (during first chemo cycle), week 6, week 20, at end of therapy, and at 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study startMay 2008
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: Low accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter M. Anderson, MD, PhD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00673179
- Sponsor's protocol ID
- 2007-0404
- Status last verified
- Sep 2014
- First submitted
- 6 May 2008
- Last updated
- 10 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy
- ClinicalTrials.gov ID
- NCT00673179
- Acronym / sponsor ID
- 2007-0404
- Conditions
- Osteosarcoma
- Keywords
- Doxorubicin, AD, Hydroxydaunomycin hydrochloride, Cisplatin, Paraplatin®, Methotrexate, Ifosfamide, Osteosarcoma
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 7 May 2008 (estimated)
- Results
- Posted 10 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. The drugs and schedules will vary depending on the status of the cancer and its level of risk for spreading, but they will include combinations of doxorubicin (non-liposomal), cisplatin, methotrexate, and ifosfamide, as described below.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Outpatient Chemotherapy | Experimental | Drug: Doxorubicin, Drug: Cisplatin, Drug: Methotrexate, Drug: Leucovorin, Behavioral: Questionnaire, Procedure: SurgeryPre-Surgery, Regimen 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m^2/day for 2 days, Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen 1: Methotrexate 12 gm/m^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m^2 twice daily, Leucovorin Rescue. |
| Additional Risk-Adapted Outpatient Chemotherapy | Experimental | Drug: Doxorubicin, Drug: Cisplatin, Drug: Methotrexate, Drug: Leucovorin, Drug: Dexrazoxane, Drug: Ifosfamide, Behavioral: Questionnaire, Drug: Gemcitabine, Drug: Sargramostim, Procedure: Surgery, Drug: MesnaPre-Surgery, Regimen 2: Dexrazoxane 900 mg/m^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m^2 (intra-arterial); Surgery; Post-Surgery, Regimen 2: Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m^2/day and Mesna 2.8 gm/m^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg). |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Newly diagnosed high-grade osteosarcoma. Patients with unresectable or metastatic disease ARE eligible.
- Age 5-40 years old on date of diagnostic biopsy.
- 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.
- Signed informed consent.
- Negative pregnancy test in females of child bearing potential, and if sexually active, willingness to use effective contraception during chemotherapy.
Key exclusion criteria (2 listed)
- Diagnosis other than osteosarcoma.
- Pregnant or lactating females, or unwilling to use effective contraception during chemotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxorubicinAlso: AD, Hydroxydaunomycin hydrochloridePre-Surgery, Regimen 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Regimen 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2. | Drug | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| CisplatinAlso: Paraplatin®Pre-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Regimen 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion. | Drug | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| MethotrexatePre-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Regimen 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours. | Drug | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| LeucovorinPre- and Post-Surgery, Regimen 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Regimen 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours. | Drug | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| DexrazoxaneAlso: ZinecardDose 900 mg/m^2 IV Push with doxorubicin. Pre-Surgery, Regimen 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7. | Drug | Additional Risk-Adapted Outpatient Chemotherapy |
| IfosfamideAlso: IfexPost-Surgery, Regimen 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2. Dose 2.8 grams m^2/day. | Drug | Additional Risk-Adapted Outpatient Chemotherapy |
| QuestionnaireAlso: SurveyQuestionnaires to be completed on 5 different days during the study. | Behavioural | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| GemcitabineAlso: Gemzar, Gemcitabine HydrochlorideIV over 1 hour, every other week. | Drug | Additional Risk-Adapted Outpatient Chemotherapy |
| SargramostimAlso: GM-CSF, Leukine™Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine. | Drug | Additional Risk-Adapted Outpatient Chemotherapy |
| SurgeryPlanned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12. | Procedure or surgery | Additional Risk-Adapted Outpatient Chemotherapy, Outpatient Chemotherapy |
| MesnaAlso: MesnexIV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2/day. | Drug | Additional Risk-Adapted Outpatient Chemotherapy |
Primary outcome
Treatment Success (6 or Fewer Hospitalizations During Front-line Chemotherapy)
Time frame: Baseline to 5 Years
Treatment success defined as a patient having 6 or fewer hospitalizations during front-line chemotherapy.
1 secondary outcome
Quality of Life (Ped QL) Assessment
Time frame: Peds QL measures at week 0 (during first chemo cycle), week 6, week 20, at end of therapy, and at 3 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter M. Anderson, MD, PhD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Doxorubicin, Cisplatin and Methotrexate in people with Osteosarcoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Success (6 or Fewer Hospitalizations During Front-line Chemotherapy) (time frame: Baseline to 5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2014.