PS-341 With Oral Temozolomide in Patients With Advanced Refractory Solid Tumors or Melanoma
| Status: | Recruiting |
|---|---|
| Conditions: | Skin Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 9/23/2012 |
| Start Date: | June 2003 |
A Phase I/II Clinical Trial of PS-341 in Combination With an Extended Continuous Oral Schedule of Temozolomide in Patients With Advanced Refractory Solid Tumors With the Phase II Component Only in Patients With Melanoma
Patients are asked to participate in this research because they have been diagnosed as
having cancer that is not curable by any standard means including surgery or radiation
therapy or other treatments. The natural history of the patient’s cancer is that the
disease will continue to spread and will cause a loss of health and eventually death. This
study will examine if two drugs Temozolomide and PS-341 can be combined and given to
patients without severe side effects. We will try to determine a dose of each medication
that is safe and can make the patient’s tumor change in a way to make it more sensitive to
chemotherapy such as Temozolomide. Our ultimate goal is to find treatment that may be
effective in treating malignant melanoma. However in the initial part of the trial,
patients with other cancers will also be allowed to go on treatment. Temozolomide has been
FDA approved for brain tumors and shown to be effective in melanoma similar to another drug
(DTIC) that is approved for melanoma. PS-341 is an investigational agent that has been
given to many patients in early trials, but its ability to shrink cancers such as melanoma
is unknown. It is a new form of cancer therapy that works by blocking the activity of
proteasomes. Proteasomes are found in all cells including cancer cells. By blocking them
we may make the cancer cell especially sensitive to chemotherapy and death. We have reason
based on test tube studies and animal experiments to believe that this combination of
Temozolomide and PS-341 may be especially effective in melanoma and we will test that in the
later part of the trial after the correct doses are defined. In the last phase of the study
between 30 and 75 patients with melanoma will be given the combination of treatments to
assess how effective it is at controlling or shrinking melanoma and how severe the side
effects are on the rest of the body. This treatment is considered investigational for
melanoma.
Inclusion Criteria:
Phase I
- Histologically proven malignancy advanced non-hematologic malignancy that is not
curable by standard surgery, radiation therapy, or chemotherapy. Patients with
melanoma, especially those with accessible tumors will be sought for this trial, but
this part of the trial will not be limited to only melanoma patients
- No available effective therapy
- Adequate performance status for the study, ECOG 0-1
- Adequate baseline organ system function,
- Agreement to use a barrier method of contraception, if potentially fertile
- Ability to understand and willingness to grant informed consent
- Patients with brain metastases are eligible only if the brain lesions are under
control for a minimum of 4 weeks, with no progressive symptoms, and off systemic
steroids. Patients with primary brain tumors are eligible if their dose of systemic
steroids is stable for at least 5 days.
- Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or
mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation
therapy. All treatment related toxicity must have resolved as well. Patients can not
receive concomitant radiation therapy
- Patients must be 18 years of age or above and competent to sign an institutionally
IRB approved informed consent Phase II Trial
- For the phase II trial, all patients must have histologically advanced and incurable
melanoma. Disease must be measurable.
- No other active malignancy including solid tumors or hematologic cancers at risk for
recurrence greater than 50% within 24 months.
- Melanoma patients can have up to 3 regimens of prior biologic therapies as adjuvant
or for disseminated disease, but only a single systemic chemotherapy regimen for
metastatic disease. Patients receiving chemotherapy in the adjuvant therapy may have
single chemotherapy regimen for advanced disease if greater than 6 months from
adjuvant therapy.
- Adequate baseline organ system function,
- Completed prior chemotherapy a minimum of 4 weeks previously (6 weeks for BCNU and/or
mitomycin C), 4 weeks for prior biologic therapy, and 2 weeks for localized radiation
therapy. No prior PS-341 is allowed. All treatment related toxicity must have
resolved as well. Patients can not receive concomitant radiation therapy
- Patients must be 18 years of age or above and competent to sign an institutionally
IRB approved informed consent.
- Patients must have documented progression over the previous 6 months by physical
exam, X-ray, CT scan or PET scan.
Exclusion Criteria:
Phase I
- Patients with Grade 2 or greater peripheral neuropathy
- Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make
patient ineligible. No prior taxanes.
- Uncontrolled or serious infection
- New York Heart Association Class III or IV heart disease or uncontrolled angina
- Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the
past 6 months
- Concurrent therapy for cancer
- Inability to comply with protocol-specified procedures Phase II Trial Component
- Patients with Grade 2 or greater peripheral neuropathy.
- Uncontrolled or serious infection
- New York Heart Association Class III or IV heart disease or uncontrolled angina
- Myocardial infarction, cerebrovascular accident, or pulmonary embolism within the
past 6 months
- Concurrent therapy for cancer
- Inability to comply with protocol-specified procedures
- Patients with brain metastases are ineligible unless the lesions have been resected,
there is no evidence of active disease and surgical resection took place a minimum of
3 months previous to enrollment.
- Above a maximum of 320 mg/m2 of CDDP for lifetime previously administered would make
patient ineligible. No prior taxanes
We found this trial at
1
site
Vanderbilt-Ingram Cancer Center The Vanderbilt-Ingram Cancer Center, located in Nashville, Tenn., brings together the clinical...
Click here to add this to my saved trials
