Thalidomide and Temozolomide or Camptothecin-11 (CPT-11) in Patients With Gliomas
Study Details
Study Description
Brief Summary
Objectives:
1.1 To determine the efficacy, as measured by 6 month progression-free survival, of therapy with thalidomide combined with CPT-11 in the treatment of patients with recurrent and/or progressive malignant gliomas.
1.2 To determine the rate of measureable clinical response in patients treated with Thalidomide and CPT-11.
1.3 To determine Thrombotic thrombocytopenic purpura (TTP), overall survival and unexpected toxicity of Thalidomide and CPT-11 used in recurrent malignant gliomas.
1.4 To determine changes in dynamic magnetic resonance imaging (MRI) as a surrogate marker for treatment effect.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Thalidomide is a drug that interferes with the growth of blood vessels. Thalidomide may help to decrease the blood supply in the tumor and make it unable to grow. CPT-11 is a drug that was designed to stop cancer cells from dividing.
All participants will take thalidomide capsules by mouth every evening at bedtime. You will begin with 1 capsule every night for the first week then increase to 2 capsules every night for a week and then 3 capsules a night for the third week. After that, you will increase the dose to 4 capsules each night for the rest of the study. The dosages may be adjusted if you experience any severe side effects.
In addition to thalidomide, you will receive treatment with CPT-11 through a continuous injection into a vein over 90 minutes once a week for 4 weeks followed by 2 weeks of rest from the drug. This 6 week period is called a course of therapy. The courses of therapy will be repeated as long as the disease is responding to treatment for up to 2 years.
THIS IS AN INVESTIGATIONAL STUDY. Both drugs are commercially available. Thalidomide and CPT-11 are FDA approved for the treatment of some cancers. The combination of these drugs is investigational.
Up to 78 participants will take part in this study. All will be enrolled at M. D. Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Thalidomide + CPT-11 Oral Thalidomide 100 mg daily for 8 weeks + CPT-11 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest. |
Drug: Thalidomide
100 mg PO (by mouth) daily for 8 weeks
Other Names:
Drug: CPT-11
125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest
Other Names:
Procedure: MRI Scan
Dynamic MRI scan with dye injection through vein, every 6 weeks
Other Names:
Procedure: Quantitative Sensory Tests (QST)
QST, every 12 weeks, to check for any nerve problems that may be present before starting treatment; by touching a small machine tests are done on feeling of touch, vibration, and temperature.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Progression Free at 6 Months With Malignant Gliomas [6 Months]
Progression-free Survival (PFS) measured as number of participants that are alive and progression-free at 6 months.
Eligibility Criteria
Criteria
Is there an age limit? No
Inclusion Criteria:
-
Patients with histologically proven supratentorial malignant primary gliomas (Glioblastoma multiforme (GBM), Gliosarcoma (GS) Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), mixed anaplastic glioma (MAG)) will be eligible for this protocol.
-
Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan after radiation therapy.
-
Patients in the GBM stratum may have had treatment for no more than 2 prior relapses; for the AA stratum, there is no limitation for the number of relapses provided all other eligibility criteria particularly the functional status are met.
-
All patients must sign an informed consent.
-
The baseline on-study MRI should be performed within 14 days prior to registration and on a stable or decreasing steroid dosage.
-
Patients having undergone recent resection of recurrent or progressive tumor will be eligible.
-
Patients must have a life expectancy > 8 weeks.
-
Patients must have a Karnofsky performance status of >= 70
-
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, cis-retinoic acid, etc. (radiosensitizer does not count). Patients who receive either Temozolomide or CPT-11 for non-therapeutic purposes (such as presurgically for obtaining pharmacology data for the agent) will be eligible for study entry provided they have recovered from the toxic effects of the agent if any.
-
Patients must have adequate bone marrow function (Absolute neutrophil count (ANC)> 1,500/mm3 and platelet count of > 100,000/mm3), adequate liver function (alanine aminotransferase (ALT or SGPT) and alkaline phosphatase <2 times normal, bilirubin <1.5 mg/dl), and adequate renal function (blood urea nitrogen (BUN) and creatinine <1.5 times institutional normal) prior to starting therapy.
-
Patients must not be pregnant and must practice adequate contraception during the study and for 2 months after participation in study.
Exclusion Criteria:
-
Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
-
Patients must not have: a) active infection b) disease that will obscure toxicity or dangerously alter drug metabolism c) serious intercurrent medical illness. d) prior recurrence with CPT-11 (for the CPT-11 + Thalidomide arm) (prior treatment with thalidomide is permitted). e) grade 2 or higher peripheral neuropathy. Patients who have received Temozolomide or CPT-11 for non-therapeutic purposes (for eg., as part of a pharmacology study without therapeutic intent) will remain eligible for enrollment into the study.
-
No exclusion to this study will be based on race. Minorities will actively be recruited to participate. The malignant glioma patient population treated at MDACC over the past year is as follows: American Indian or Alaskan Native - 0 Asian or Pacific Islander - <2% Black, not of Hispanic Origin - 3% Hispanic - 6% White, not of Hispanic Origin - 88% Other or Unknown - 2% Total-100%
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | U.T.M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Celgene Corporation
Investigators
- Principal Investigator: Vinay K. Puduvalli, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- DM02-595
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: October 13, 2003 to October 22, 2008. All participants were recruited at UT MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | Of the 78 participants enrolled, three (3) were considered not evaluable. |
| Arm/Group Title | Glioblastoma Multiforme: Thalidomide + CPT-11 | Anaplastic Gliomas: Thalidomide + CPT-11 |
|---|---|---|
| Arm/Group Description | Oral Thalidomide 100 mg daily for 8 weeks + CPT-11 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest. | Oral Thalidomide 100 mg daily for 8 weeks + CPT-11 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest. |
| Period Title: Overall Study | ||
| STARTED | 33 | 45 |
| COMPLETED | 33 | 42 |
| NOT COMPLETED | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Glioblastoma Multiforme: Thalidomide + CPT-11 | Anaplastic Gliomas: Thalidomide + CPT-11 | Total |
|---|---|---|---|
| Arm/Group Description | Oral Thalidomide 100 mg daily for 8 weeks + CPT-11 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest. | Oral Thalidomide 100 mg daily for 8 weeks + CPT-11 125 mg/m^2 by vein weekly over 90 minutes for 4 weeks, followed by 2 weeks rest. | Total of all reporting groups |
| Overall Participants | 33 | 45 | 78 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
31
93.9%
|
41
91.1%
|
72
92.3%
|
| >=65 years |
2
6.1%
|
4
8.9%
|
6
7.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
8
24.2%
|
19
42.2%
|
27
34.6%
|
| Male |
25
75.8%
|
26
57.8%
|
51
65.4%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
33
100%
|
45
100%
|
78
100%
|
Outcome Measures
| Title | Number of Participants Progression Free at 6 Months With Malignant Gliomas |
|---|---|
| Description | Progression-free Survival (PFS) measured as number of participants that are alive and progression-free at 6 months. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 7 participants enrolled were not evaluated as they were evaluable for toxicity only (not having completed the first cycle/clinical decline/etc.). |
| Arm/Group Title | Participants With Recurrent Malignant Gliomas |
|---|---|
| Arm/Group Description | The endpoints combined results of all strata (Arm 1 of Glioblastoma Multiforme: Thalidomide + CPT-11 and Arm 2 of Anaplastic Gliomas: Thalidomide + CPT-11). |
| Measure Participants | 68 |
| Number [participants] |
24
72.7%
|
Adverse Events
| Time Frame | 4 years and 11 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Patients With Recurrent Malignant Gliomas | |
| Arm/Group Description | The endpoints combined results of all strata | |
All Cause Mortality |
||
| Patients With Recurrent Malignant Gliomas | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Patients With Recurrent Malignant Gliomas | ||
| Affected / at Risk (%) | # Events | |
| Total | 35/75 (46.7%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 1/75 (1.3%) | 1 |
| Leukopenia | 2/75 (2.7%) | 2 |
| Neutropenia | 5/75 (6.7%) | 5 |
| Gastrointestinal disorders | ||
| Nausea | 3/75 (4%) | 3 |
| Vomiting | 3/75 (4%) | 4 |
| Diarrhea | 9/75 (12%) | 10 |
| Colitis | 2/75 (2.7%) | 2 |
| Dehydration | 5/75 (6.7%) | 6 |
| Enteritis | 1/75 (1.3%) | 1 |
| Fecal incontinence | 1/75 (1.3%) | 1 |
| General disorders | ||
| Fatigue | 1/75 (1.3%) | 1 |
| Fever | 2/75 (2.7%) | 2 |
| Infections and infestations | ||
| Cellulitis | 1/75 (1.3%) | 1 |
| Infection | 3/75 (4%) | 3 |
| Pneumonia | 3/75 (4%) | 3 |
| Sepsis | 1/75 (1.3%) | 1 |
| Injury, poisoning and procedural complications | ||
| Subdural fluid collection | 1/75 (1.3%) | 1 |
| Investigations | ||
| Elevated ALT | 1/75 (1.3%) | 1 |
| Elevated Creatinine | 1/75 (1.3%) | 1 |
| Hyperglycemia | 1/75 (1.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculo-skeletal leg cramps | 1/75 (1.3%) | 1 |
| Weakness | 3/75 (4%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Death | 6/75 (8%) | 6 |
| Nervous system disorders | ||
| Seizure | 8/75 (10.7%) | 11 |
| Ataxia | 2/75 (2.7%) | 2 |
| Cerebral edema | 2/75 (2.7%) | 2 |
| Depressed level of consciousness | 1/75 (1.3%) | 1 |
| Encephalopathy | 1/75 (1.3%) | 1 |
| Hydrocephalus | 1/75 (1.3%) | 1 |
| Somnolence | 3/75 (4%) | 3 |
| Syncope | 1/75 (1.3%) | 1 |
| Psychiatric disorders | ||
| Confusion | 1/75 (1.3%) | 1 |
| Renal and urinary disorders | ||
| Urinary retention | 1/75 (1.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 2/75 (2.7%) | 2 |
| Respiratory failure | 1/75 (1.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/75 (1.3%) | 1 |
| Vascular disorders | ||
| Thrombus pulmonary embolus | 5/75 (6.7%) | 5 |
| Thrombus - deep vein thrombosis | 6/75 (8%) | 6 |
| Hypotension | 1/75 (1.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Patients With Recurrent Malignant Gliomas | ||
| Affected / at Risk (%) | # Events | |
| Total | 65/75 (86.7%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 5/75 (6.7%) | 11 |
| Anemia/decreased hemoglobin | 57/75 (76%) | 195 |
| Leukopenia | 65/75 (86.7%) | 315 |
| Lymphopenia | 52/75 (69.3%) | 284 |
| Neutrophils, absolute count | 55/75 (73.3%) | 249 |
| Thrombocytopenia | 25/75 (33.3%) | 52 |
| Endocrine disorders | ||
| Cushingoid | 11/75 (14.7%) | 11 |
| Eye disorders | ||
| Blurred vision | 12/75 (16%) | 19 |
| Gastrointestinal disorders | ||
| Abdominal cramping | 9/75 (12%) | 18 |
| Anorexia | 22/75 (29.3%) | 25 |
| Constipation | 46/75 (61.3%) | 91 |
| Dehydration | 14/75 (18.7%) | 16 |
| Diarrhea | 46/75 (61.3%) | 171 |
| Mucositis | 10/75 (13.3%) | 13 |
| Nausea | 38/75 (50.7%) | 119 |
| Pain, abdominal | 17/75 (22.7%) | 34 |
| Vomiting | 22/75 (29.3%) | 57 |
| General disorders | ||
| Dry mouth | 9/75 (12%) | 13 |
| Edema | 31/75 (41.3%) | 42 |
| Fatigue | 63/75 (84%) | 143 |
| Fever without neutropenia | 11/75 (14.7%) | 16 |
| Insomnia | 18/75 (24%) | 24 |
| Infections and infestations | ||
| Infection | 23/75 (30.7%) | 26 |
| Investigations | ||
| Alkaline Phosphatase increased | 11/75 (14.7%) | 18 |
| ALT increased | 17/75 (22.7%) | 40 |
| AST elevated | 12/75 (16%) | 19 |
| Bicarbonate sodium, low | 16/75 (21.3%) | 30 |
| Bilirubin elevated | 5/75 (6.7%) | 5 |
| BUN elevated | 12/75 (16%) | 20 |
| Cholesterol elevated | 11/75 (14.7%) | 11 |
| CPK elevated | 4/75 (5.3%) | 5 |
| Creatinine elevated | 9/75 (12%) | 11 |
| Elevated chloride | 18/75 (24%) | 38 |
| Elevated CO2 | 14/75 (18.7%) | 27 |
| Elevated AST | 6/75 (8%) | 8 |
| Hyperuricemia | 7/75 (9.3%) | 9 |
| Hypokalemia | 24/75 (32%) | 47 |
| Hypomagnesium | 13/75 (17.3%) | 16 |
| Hyponatremia | 19/75 (25.3%) | 34 |
| Hypophosphatemia | 24/75 (32%) | 56 |
| Low protein | 15/75 (20%) | 21 |
| Metabolism and nutrition disorders | ||
| Hyperglycemia | 49/75 (65.3%) | 130 |
| Hypoalbuminemia | 23/75 (30.7%) | 53 |
| Hypocalcemia | 21/75 (28%) | 57 |
| Weight gain | 10/75 (13.3%) | 12 |
| Weight loss | 12/75 (16%) | 15 |
| Musculoskeletal and connective tissue disorders | ||
| Muscle weakness lower extremity | 25/75 (33.3%) | 36 |
| Muscle weakness facial | 6/75 (8%) | 7 |
| Muscle weakness left or right sides | 7/75 (9.3%) | 7 |
| Muscle weakness generalized | 15/75 (20%) | 21 |
| Pain, back | 6/75 (8%) | 7 |
| Pain, chest (non cardiac) | 6/75 (8%) | 7 |
| Pain, extremity | 9/75 (12%) | 18 |
| Nervous system disorders | ||
| Ataxia | 6/75 (8%) | 9 |
| Cognitive disturbance | 8/75 (10.7%) | 8 |
| Dizziness | 32/75 (42.7%) | 55 |
| Dysphasia | 5/75 (6.7%) | 5 |
| Gait/walking | 31/75 (41.3%) | 37 |
| Memory Impairment | 26/75 (34.7%) | 29 |
| Neuropathy motor | 11/75 (14.7%) | 14 |
| Neuropathy sensory | 35/75 (46.7%) | 52 |
| Pain, headache | 39/75 (52%) | 75 |
| Pyramidal tract dysfunction | 19/75 (25.3%) | 27 |
| Seizure | 25/75 (33.3%) | 48 |
| Somnolence | 20/75 (26.7%) | 25 |
| Speech impairment | 19/75 (25.3%) | 28 |
| Tremors | 18/75 (24%) | 22 |
| Psychiatric disorders | ||
| Confusion | 16/75 (21.3%) | 22 |
| Mood alteration | 18/75 (24%) | 20 |
| Renal and urinary disorders | ||
| Incontinence, urinary | 8/75 (10.7%) | 8 |
| Urinary frequency | 13/75 (17.3%) | 13 |
| Respiratory, thoracic and mediastinal disorders | ||
| Allergic rhinitis | 11/75 (14.7%) | 16 |
| Cough | 24/75 (32%) | 33 |
| Dyspnea | 16/75 (21.3%) | 21 |
| Nasal/paranasal reactions | 6/75 (8%) | 7 |
| Skin and subcutaneous tissue disorders | ||
| Acne | 12/75 (16%) | 17 |
| Alopecia | 13/75 (17.3%) | 13 |
| Bruising (without thrombocytopenia) | 5/75 (6.7%) | 5 |
| Dry skin | 16/75 (21.3%) | 17 |
| Vascular disorders | ||
| Hypotension | 9/75 (12%) | 10 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Vinay Puduvalli, MD / Associate Professor |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | 713-745-5769 |
| kuhunter@mdanderson.org |
- DM02-595