MDACC Study Summary 2009-0357

Study Summary
No. 2009-0357:.......Melanoma......Agop Y. Bedikian......Melanoma Medical Oncology

Study Summary Title



Study Summary Number:	2009-0357

Study Title:	A Phase I/II Open-Label Study TPI 287 in Combination with Temozolomide in Patients with Metastatic Melanoma

Physician

New Patient Referral



Name:	Agop Y. Bedikian	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Melanoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2921 Contact us about clinical trials

General Information



Disease Group:	Melanoma	Supported By:	Archer Biosciences

Phase of Study:	Phase I/Phase II	Return Visit:	Every 4 weeks

Treatment Agents:	Temozolomide TPI 287	Home Care:	N/A

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of the Phase I portion of this study is to find the highest tolerable dose of TPI 287 that can be given in combination with Temodar (temozolomide) to patients with metastatic melanoma. The goal of the Phase II portion of this study is to learn if TPI 287, given in combination with temozolomide, can control metastatic melanoma. The safety of this combination will also be studied.

Study Objectives / Outcomes

OBJECTIVES

Phase I portion of study

To determine the Maximum Tolerated Dose (MTD), as measured by clinical and laboratory adverse events, for the administration of TPI 287 administered weekly for three weeks out of every four, and then combined with temozolomide (Temodar) in patients with metastatic melanoma.

Phase II portion of study

1. Primary objective: To estimate the efficacy of TPI 287 – temozolomide combination as measured by percent of patients without tumor progression at 6 months,

2. Secondary objectives:

a. To evaluate the response rate, response duration, median progression-free survival (PFS), overall survival of patients with metastatic melanoma treated with TPI 287 – temozolomide combination.

b. To determine the long-term toxicity of TPI 287, administered intravenously on days 1, 8 and 15 (+/- 1 day) every four weeks plus temozolomide, given orally, once a day for five days every cycle (Days 1 through 5 [+1 day]) for the treatment of patients with metastatic melanoma.

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	02/03/2010

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients with histologically proven melanoma with metastasis that is unresectable Stage III or Stage IV. This will include bulky stage III and M1-3. Patients with melanoma with documented metastases to the brain are eligible.

2) Patients must have shown unequivocal evidence for tumor recurrence or progression and should have at least one indicator lesion, that can be measured in one dimension as >/=20mm with conventional techniques (CT, MRI, X-ray) or >/=10mm with spiral CT scan.

3) Patients may have had up to two prior cytotoxic chemotherapy regimens for their disease (immunological or targeted therapy e.g. vaccine, IL-2, B-RAF inhibitors, will not be considered prior cytotoxic chemotherapy). Patient should not have been treated with Docetaxel, Paclitaxel or other taxanes.

4) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.

5) Patients must have a Eastern Cooperative Oncology Group status of </=2.

6) Patients must have recovered from the toxic effects of prior therapy: 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.

7) Patients must have adequate bone marrow function (ANC >/= 1,500/mm3 and platelet count of >/= 100,000/mm3), adequate liver function (SGPT and SGOT </= 2.5 times normal, bilirubin </= 2 mg/dl), and adequate renal function (BUN and creatinine </=1.5 times institutional normal) prior to starting therapy.

8) TPI 287 may interfere with coumadin dosing and patients who are taking this combination will require monitoring of their PT, PTT and INR.

9) Females of childbearing potential (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized) must use acceptable contraceptive methods (abstinence, intrauterine device, oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.

10) Patient should be 15 years of age or older

Exclusion Criteria:

1) Patients with brain metastases must not be taking primidone, carbamazapine, phenobarbital or phenytoin anticonvulsants (Enzyme-Inducing Anti-Epileptic Drugs). Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week.

2) Patients with any neuropathy.

3) Patients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, history of myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.

4) Because of the concerns of potentially harmful interactions of TPI 287and other medications taken by patients who are HIV positive or have AIDS related diseases, patients who are HIV positive are not be eligible for entry into this study. Only patients with suspected HIV will be tested and if positive, will be ineligible.

5) Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) are ineligible for Phase II part of the study unless in complete remission and off of all therapy for that disease for a minimum of 3 years. However, during Phase I part of the study, a patient with second malignancy is eligible if that malignancy has not recurred after appropriate therapy.

6) Patients with: a) active infection, b) disease that will obscure toxicity or dangerously alter drug metabolism, c) serious intercurrent medical illness, d) prior documented recurrence with temozolomide

7) Females who are pregnant or breastfeeding.

8) Patients younger than 15 years of age

9) Patients with prior therapy with paclitaxel or other taxanes.

Links

Registration Number: NCT01067066
Study Information on Clinical Trials Registry (clinicaltrials.gov)