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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cortice Biosciences, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01067066
First received: February 9, 2010
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: TPI 287
Drug: Temodar (Temozolomide)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Open-Label Study TPI 287 in Combination With Temozolomide in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of TPI 287 in Combination with Temodar [ Time Frame: 28 day study cycle ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Response rate provided along with a 95% credible interval. Logistic regression models used to assess the association between progression-free survival at 6 months and covariates of interest. Additionally, Cox proportional hazards regression models will be fit to model the association between progression-free survival and the same covariates. Simon's minimax two-stage design used to evaluate the response rate.


Estimated Enrollment: 106
Study Start Date: February 2010
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TPI 287 + Temodar
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
Starting dose cycle 1, 90 mg/m2 by vein (IV) on Days 1, 8, 15 (+/- 1 day)
Drug: Temodar (Temozolomide)
Starting dose cycle 1, 85 mg/m^2 by mouth (PO) daily, Day 1 to 5.
Other Name: Temozolomide

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, 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.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01067066

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Cortice Biosciences, Inc.
Investigators
Study Chair: Agop Y. Bedikian, MD, BS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01067066     History of Changes
Other Study ID Numbers: 2009-0357, NCI-2011-00558
Study First Received: February 9, 2010
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
TPI 287
microtubule inhibitor
Temozolomide
Temodar
cytotoxic agent
unresectable Stage III
Stage IV
Metastatic Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014