A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma

NCT01067066 | Terminated Phase 1

• 2 other identifiers: 2009-0357NCI-2011-00558
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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. NOTE: Study stopped before progressing to Phase II portion.

Conditions

Melanoma

Keywords

TPI 287; microtubule inhibitor; Temozolomide; Temodar; cytotoxic agent; unresectable Stage III; Stage IV; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of TPI 287 in Combination with Temodar

  MTD is highest dose level in which 6 patients treated with at most 1 experiencing dose limiting toxicity (DLT). Maximum Tolerated Dose (MTD), measured by clinical and laboratory adverse events.

  28 day study cycle

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  6 months

Study Arms (1)

TPI 287 + Temodar

EXPERIMENTAL

Starting dose of TPI 287 90 mg/m\^2 IV on Days 1, 8, 15 + Temozolomide (Temodar) PO at 85 mg/m\^2 on Days 1-5.

Drug: TPI 287; Drug: Temodar (Temozolomide)

Interventions

TPI 287 DRUG

Starting dose cycle 1, 90 mg/m2 by vein (IV) on Days 1, 8, 15 (+/- 1 day)

TPI 287 + Temodar

Temodar (Temozolomide) DRUG

Starting dose cycle 1, 85 mg/m\^2 by mouth (PO) daily, Day 1 to 5.

Also known as: Temozolomide

TPI 287 + Temodar

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• Patients must have a Eastern Cooperative Oncology Group status of \</=2.
• 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.
• Patients must have adequate bone marrow function (ANC \>/= 1,500/mm3 and platelet count of \>/= 100,000/mm3), adequate liver function (SGPT and serum glutamate oxaloacetate transaminase (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.
• TPI 287 may interfere with coumadin dosing and patients who are taking this combination will require monitoring of their PT, PTT and international normalized ratio (INR).
• 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.
• Patient should be 15 years of age or older

You may not qualify if:

• Patients with brain metastases must not be taking primidone, carbamazepine, 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.
• Patients with any neuropathy.
• 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.
• 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.
• 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.
• 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
• Females who are pregnant or breastfeeding.
• Patients younger than 15 years of age
• Patients with prior therapy with paclitaxel or other taxanes.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Cortice Biosciences, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

TPI-287; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rodabe N Amaria, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2010
• First Posted: February 11, 2010
• Study Start: February 3, 2010
• Primary Completion: July 6, 2016
• Study Completion: July 6, 2016
• Last Updated: July 21, 2017

Record last verified: 2017-07

Locations

US (1)