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Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma


Phase 1/Phase 2
15 Years
N/A
Not Enrolling
Both
Sarcoma

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Trial Information

Phase I Dose Escalation of Monthly Intravenous Ra-223 Dichloride in Osteosarcoma


Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 3 groups of 3 participants will be enrolled
in the Phase I portion of the study, and up to 6 participants will be enrolled in Phase II.

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of radium-223 dichloride based on when you join this study. The first group of
participants will receive the lowest dose level. Each new group will receive a higher dose
than the group before it, if no intolerable side effects were seen. This will continue
until the highest tolerable dose of radium-223 dichloride is found.

If you are enrolled in the Phase II portion, you will receive radium-223 dichloride at the
highest dose that was tolerated in the Phase I portion.

Study Drug Administration:

You will receive radium-223 chloride by vein over several minutes on Day 1 of each 4-week
cycle.

You should drink plenty of fluids before each study drug dose.

You and your caregivers will receive spoken and written instructions about safety
precautions after receiving this drug.

Study Visits:

At all study visits, you will be asked about any drugs you may be taking and if you have had
any side effects from them.

On Day 1 of Cycle 2-6:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

Within 1-3 weeks after Cycle 3:

- You will have scans such as a bone scan and CT or MRI scan to check the status of the
disease.

- Blood (about 1 tablespoon) will be drawn for routine tests.

You may have other routine tests done, including a pregnancy test, if the study doctor
thinks it is needed.

Length of Study Drug Dosing:

You may continue taking the study drug for up to 6 cycles. You will no longer be able to
take the study drug if the disease gets worse, if intolerable side effects occur, or if you
are unable to follow study directions.

Your participation in this study will be over once you have completed the end-of-dosing
visit (and follow-up visits if applicable).

End-of-Dosing Visit:

About 30 days after your last study drug dose:

- You will be asked about any drugs you may be taking and if you have had any side
effects from them.

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have scans such as a bone scan and CT or MRI scan to check the status of the
disease.

Follow-Up Visits:

If you are younger than 18 years old, your height and weight will be measured 1 time a year
until you turn 21. These measurements may stop earlier if your height stays about the same
for 2 years in a row.

This is an investigational study. Radium-223 dichloride is not FDA approved or commercially
available. It is currently being used for research purposes only.

Up to 15 patients will be enrolled in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e.
high-risk only) with no standard curative options available with at least one
indicator lesion avid on 99mTc-MDP scan will be eligible

2. Anatomic imaging (CT or MRI) of all sites of disease along with chest CT at baseline
and restaging for all patients will be done to allow for assessment of RECIST
progression. RECIST progression will determine progressive disease regardless of
other imaging.

3. Indicator lesion that has uptake of 99mTc-MDP on bone scan and can be subjected to
quantitative assessment by this scans and possibly other means.

4. Age 15 and above and >40 kg.

5. ECOG=2 or better

6. Subjects or their guardians must be able to understand and be willing to sign the
written informed consent form. A signed informed consent form must be appropriately
obtained prior to the conduct of any trial-specific procedure.

7. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade
1 or less at the time of signing the Informed Consent Form (ICF).

8. Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of study drug. Post-menopausal women (defined as no
menses for at least 1 year) and surgically sterilized women are not required to
undergo a pregnancy test.

9. Subjects (men and women) of childbearing potential must agree to use adequate
contraception beginning at the signing of the ICF until at least 30 days after the
last dose of study drug. The definition of adequate contraception will be based on
the judgment of the principal investigator or a designated associate.

10. Acceptable hematology and serum biochemistry screening values: White Blood Cell Count
(WBC) >= 1500/mm3; Absolute Neutrophil Count (ANC) >= 1,000/mm3; Platelet (PLT) count
>= 75,000/mm3; Hemoglobin (HGB) >= 8 g/dl; Total bilirubin level <= 1.5 x
institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) <= 2.5 x ULN; Creatinine <= 1.5 x ULN; Albumin > 25
g/L

11. Willing and able to comply with the protocol, including follow-up visits and
examinations.

12. Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e.
high-risk only) with at least one indicator lesion avid on 99mTc-MDP scan will be
eligible.

Exclusion Criteria:

1. Diagnosis other than osteosarcoma.

2. 99mTc-MDP bone scan with no significant uptake (i.e. "nothing" for a bone-seeking
isotope to target/ i.e. indicator lesion that would be expected to have the
bone-seeking targeted uptake of 223-radium dichloride).

3. Other malignancy treated within the last 3 years (except non-melanoma skin cancer or
low-grade superficial bladder cancer).

4. Any other serious illness or medical condition, such as but not limited to: Any
active infection ≥ National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE) version 4.03 Grade 2; Cardiac failure New York Heart Association
(NYHA) III or IV; Fecal incontinence (this is because of Ra-223 elimination in
feces).

5. Women who are pregnant or breast-feeding.

6. Inability to comply with the protocol and/or not willing or not available for
follow-up assessments.

7. Any condition which, in the investigator's opinion, makes the subject unsuitable for
trial participation.

8. Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, biologic therapy, or tumor embolization)

9. Patients on oxygen.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

If at least 2 patients are observed to have a dose-limiting toxicity (DLT), the MTD will have been exceeded and no further patients will be enrolled at this dose level or at any higher dose level. The prior dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). A tentative MTD becomes final when a total of 6 patients are treated with less than 2 showing DLT. Dose-limiting toxicities include all adverse experiences that are related to study medication, and clearly not related to disease progression or intercurrent illness.

Outcome Time Frame:

3 months

Safety Issue:

Yes

Principal Investigator

Vivek Subbiah, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2012-0952

NCT ID:

NCT01833520

Start Date:

October 2013

Completion Date:

Related Keywords:

  • Sarcoma
  • Sarcoma
  • Osteosarcoma
  • recurrent or metastatic
  • Ra-223 dichloride
  • Radium-223 chloride
  • Alpharadin
  • Osteosarcoma
  • Sarcoma

Name

Location

University of Texas MD Anderson Cancer CenterHouston, Texas  77030