Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 12 and over Other 2007-0515 NCT00615680

Trial Description

Summary

Primary Objectives:

1. To determine the overall objective response rate of R1507 in patients with recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas of the following subtypes: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.

2. To determine the progression-free survival at 18 weeks from start of treatment of patients with progressive, recurrent or refractory Ewing's sarcoma (Ewing's family of tumors) treated with R1507.

Secondary Objectives:

1. To estimate the duration of response, progression-free survival rate at 18 weeks from start of treatment and overall progression-free survival of patients with recurrent or refractory, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas of the following subtypes: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma who were treated with R1507.

2. To determine the overall objective response rate, response duration, overall progression-free survival and overall survival of patients with progressive, recurrent or refractory Ewing's sarcoma (Ewing's family of tumors) treated with R1507.

3. To define the population pharmacokinetic profile of R1507 in selected study patients.

4. To define the tolerability and adverse event profile of R1507 in sarcoma patients.

Exploratory Objectives:

1. To explore changes in PET scans in patients treated with R1507.

2. To explore serum biomarkers and their potential correlations with pharmacokinetics and clinical response.

Further Study Information

THE STUDY DRUG:

R1507 is a human monoclonal antibody designed to inhibit (turn off) tumor growth.

SCREENING TESTS:

Before you can start treatment on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

• Your medical history will be recorded.

• You will be asked about any drugs you may be taking.

• You will have a physical exam.

• Blood (about 1 teaspoon) and urine will be collected for routine tests.

• To check the status of the disease, you will have a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan.

• You will have a positron emission tomography (PET) scan.

• Tissue samples collected during an earlier surgery or biopsy will be sent to check your original diagnosis. If samples are not available, you will have a tumor biopsy. This procedure will be described to you in more detail by the study doctor.

• Women who are able to have children must have a negative urine or blood (about 1 teaspoon) pregnancy test.

STUDY DRUG ADMINISTRATION:

If you are found to be eligible to take part in this study, you will receive R1507 through a vein 1 time a week. The first dose will be given over 90 minutes. If this dose is well tolerated, other doses will be given over 60 minutes.

If your doctor thinks it is in your best interest, you will receive a central venous catheter (CVC). This procedure will be described to you in more detail and you will sign a separate consent form.

STUDY VISITS:

Before you receive the study drug on Day 1 and Weeks 4 and 12, blood (about 1 teaspoon each time) will be drawn for antibody testing.

On Weeks 1 and 6 you will have electrocardiograms (ECGs -- tests that measures the electrical activity of the heart) before and after you receive the study drug.

Every week while on study, your vital signs and weight will be measured. You will be asked about any side effects you may have experienced.

Every week for the first 6 weeks and then every 3 weeks after that, you will have a physical exam. Blood (about 1 teaspoon) will be drawn for routine tests.

Every month, women who are able to have children will have a urine or blood (about 1 teaspoon) pregnancy test.

Every 6 weeks for the first 24 weeks and then every 12 weeks after that, you will have a CT scan or MRI to check the status of the disease.

On Weeks 2, and 12, or 18, you will have a fluorodeoxyglucose-positron emission tomography (FDG-PET) scan.

LENGTH OF STUDY:

You may continue to receive the study drug for as long as you are benefitting. You will be taken off study early if the disease gets worse, you have intolerable side effects, or if your doctor thinks that it is in your best interest.

END-OF-TREATMENT VISIT:

Once you are no longer receiving the study drug, you will have an end-of-treatment visit within 7 days after your last dose. At this visit, the following tests and procedures will be performed:

• You will have a physical exam, including measurement oft your vital signs

• You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

• Blood (about 1 teaspoon) will be drawn for routine tests.

• Urine will be collected for routine tests.

• You will have an ECG.

• You will be asked about any drugs you may be taking.

• If you have not had one in the last 6 weeks, you will have an x-ray to check the status of the disease.

• Blood (about 1 teaspoon) will be drawn for antibody tests.

FOLLOW-UP VISITS:

Six (6) and 12 weeks after your last dose of study drug, blood (about 1 teaspoon each time) will be drawn for antibody tests.

If you are experiencing side effects when you leave the study, you may have follow-up visits for up to 30 days. The number of follow-up visits and the tests that may be performed will be decided by your doctor.

After you complete all study treatments, you will receive phone calls every 3 months to ask about the status of the disease. The phone call should take about 5-10 minutes.

This is an investigational study. R1507 is not FDA approved or commercially available. At this time, R1507 is only being used in research

During the study, there will be no cost to you for R1507 or for any tests or procedures that are only performed because you are part of this research study (such as FDG-PET scans and ECG's).

Up to 245 patients will take part in this multicenter study. Up to 50 patients will be enrolled at M. D. Anderson.

Eligibility Criteria

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed Ewing's sarcoma (Ewing's family of tumors ESFT), Osteosarcoma, Synovial sarcoma, Rhabdomyosarcoma. Other sarcomas of the following subtypes: Alveolar soft part sarcoma, Desmoplastic small round cell tumors, Extraskeletal myxoid chondrosarcoma, Clear cell sarcoma, Myxoid Liposarcoma.

2. Patients must have had histological verification of malignancy by central pathology review (to be completed within 6 weeks of study entry).

3. All patients must have recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator. For the patients with Ewing's and ESFT subtype, patients must have documented progressive disease by WHO criteria.

4. Age >/= 12 years.

5. Life expectancy of at least 6 weeks.

6. Karnofsky performance status of >/= 70%

7. Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease and lesions seen on PET scan only are not considered measurable.

8. Adequate organ function requirements defined as: Bone marrow (in the absence of bone marrow involvement by neoplasia), Absolute neutrophil count >/= 1.5 x 10^9/L (being >/= 30 days off growth factors), Platelet count >/= 75,000/mL *in patients with documented bone marrow involvement by neoplasia, no minimum ANC or platelet count is necessary at the discretion of the investigator.

9. Hepatic-Total bilirubin </= 1.5 times the ULN for age. ALT/AST (SGPT/SGOT) </= 3x the ULN for the reference lab( </= 5x the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age)

10. Renal-Creatinine clearance >/= 70 ml/min/1.73m2 or Serum creatinine < 1.5 x ULN per age.

11. Prior Therapy-Time elapsed from previous therapy must be >/= 3 weeks. Patients must be recovered from the effects of any prior surgery, radiotherapy or systemic therapy, including any investigational therapy.

12. Patients who have undergone autologous hematopoietic stem cell transplantation (HSCT) will be eligible once they have recovered from all toxicities from therapy (</= grade 1 except for alopecia). Patients who have received allogenic HSCT will be eligible 6 months after the procedure provided there is no evidence of active graft-versus-host disease and immunosuppressive treatment has been discontinued for at least 30 days.

13. Patients with CNS disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of neurological deficit and are >/= 6 weeks from completion of brain irradiation.

14. Patients or their legal representative must be able to read, understand and provide written informed consent to participate in the trial. Patients younger than 18 years of age should provide assent to participate in the trial.

15. Females of childbearing potential as well as fertile males and their partners must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication. An effective form of contraception is use of an oral contraceptive, a double barrier method, or commitment to sexual abstinence.

16. Diabetic patients must have well controlled disease. Controlled disease is considered if there has been no change in medications (oral or insulin) greater than 10% for the past 30 days. There should be no sign or symptom of ketosis at enrollment or within 30 days prior to enrollment.

17. The ESFT population for whom the time from diagnosis to first relapse is </= 24 months, patients must have received at least two distinct chemotherapy programs (one for initial systemic therapy and a second for first relapse) and be surgically unresectable.

Exclusion Criteria:

1. Clinically significant unrelated systemic illness (such as serious infections requiring active systemic therapy; cardiovascular disease [congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension], poorly controlled diabetes, hepatic renal or other organ dysfunction) which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.

2. Known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies.

3. Concomitant use of any other investigational agent(s). An investigational therapy is defined as treatment for which there is currently no approved indication from regulatory authorities. Prior use of investigational agent(s), is acceptable if at least 3 weeks have elapsed since last dose and no future doses are planned.

4. Current or previous treatment (within the past 6 months) with chronic, pharmacologic doses of corticosteroids, immunosuppressive agents or medications that inactivate or may interfere with the pharmacologic activity of R1507.

5. Current or prior therapy with IGF inhibitor (monoclonal or specific kinase inhibitor).

6. Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since final menstrual period) must have a negative pregnancy test within 7 days prior to first dose.

7. History of solid organ transplant.

8. Other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Dejka M. Araujo, MD

Principal Investigator

Dejka M. Araujo, MD

Ph: 713-792-3626

U.S.A.
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Dejka M. Araujo, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00615680
Information obtained from ClinicalTrials.gov on February 27, 2008