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A Phase I, Open Label Study of AT-101 Plus Radiotherapy and Temozolomide and of AT-101 Plus Adjuvant Temozolomide for Patients With Newly-Diagnosed Glioblastoma Multiforme

Phase 1
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

A Phase I, Open Label Study of AT-101 Plus Radiotherapy and Temozolomide and of AT-101 Plus Adjuvant Temozolomide for Patients With Newly-Diagnosed Glioblastoma Multiforme



- Determine the maximum tolerated dose (MTD) of gossypol (AT-101) when administered with
radiotherapy (RT) and concurrent temozolomide (TMZ) in patients with newly diagnosed
glioblastoma multiforme.

- Determine the MTD of gossypol when administered with adjuvant TMZ after standard RT and
concurrent TMZ in these patients.


- Assess the toxicity of these treatment regimens.

- Assess and describe the pharmacokinetics of gossypol.

- Determine, preliminarily, the therapeutic activities of these regimens.

- Determine the relationship between these regimens and cellular and molecular features
identified in tumor biopsy specimens.

OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of
gossypol. Patients are assigned to 1 of 2 treatment groups. Patients who participate in
group I are NOT eligible for group II.

- Group I: Patients receive oral gossypol and undergo radiotherapy once daily 5 days a
week for up to 6 weeks. Patients also receive oral temozolomide once daily for up to 6
weeks. Treatment continues in the absence of disease progression or unacceptable

- Group II: Patients receive oral temozolomide on days 1-5 and oral gossypol once daily
on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.

Cohorts of 3-10 patients per treatment group receive escalating doses of gossypol until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6
or 3 of 10 patients experience dose-limiting toxicity.

Patients undergo blood collection periodically for pharmacokinetic studies. Tumor tissue
samples are examined for biomarkers including, but not limited to, Bcl-2 family protein
expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain), MGMT gene methylation
status, and gene expression array.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma

- Meets 1 of the following criteria:

- Completed surgery within the past 6 weeks (group I)

- Received radiotherapy and concomitant temozolomide at least 4 weeks but no more
than 7 weeks prior to start of study treatment (group II)

- Must be on a stable corticosteroid regimen (no increase for 5 days)


- Karnofsky performance status 60-100%

- Hemoglobin ≥ 10 g/dL

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Creatinine ≤1.5 mg/dL

- Bilirubin ≤ 1.5 mg/dL

- ALT and AST ≤ 2.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 months after
completion of study treatment

- Mini Mental State Exam score ≥ 15

- Must be able to swallow and retain oral medication

- No serious concurrent infection or medical illness that would preclude study

- No other malignancy within the past 5 years, except for curatively treated carcinoma
in situ or basal cell carcinoma of the skin

- No sensory neuropathy ≥ grade 2

- No allergies to gossypol

- No symptomatic hypercalcemia or hypercalcemia > grade 2

- No gastrointestinal disease including any of the following:

- Malabsorption syndrome

- Disease significantly affecting gastrointestinal function

- Ulcerative colitis

- Inflammatory bowel disease

- Partial or complete small bowel obstruction


- See Disease Characteristics

- Recovered from the immediate postoperative period

- No prior radiotherapy, chemotherapy, immunotherapy, therapy with biologic agents
(including immunotoxins, immunoconjugates, antisense agents, peptide-receptor
antagonists, interferons, interleukins, tumor-infiltrating lymphocyte therapy,
lymphokine-activated killer cells or gene therapy), or hormonal therapy for this
brain tumor (group I)

- Prior glucocorticoid therapy allowed

- No prior polifeprosan 20 with carmustine implant (Gliadel wafers) (group I)

- No prior gossypol

- No prior radiosurgery or brachytherapy

- No prior resection of the stomach or small intestine

- No other concurrent anticancer therapy (i.e., chemotherapeutics or investigational

- No concurrent cytochrome p450 enzyme-inducing anticonvulsant drugs

- No concurrent prophylactic filgrastim (G-CSF)

- No concurrent iron supplements

- Nutritional supplements containing iron allowed

- No concurrent intensity-modulated radiotherapy

- No concurrent electron, particle, implant, or stereotactic radiosurgery boost

Type of Study:


Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Safety Issue:


Principal Investigator

John Fiveash, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Alabama at Birmingham


United States: Food and Drug Administration

Study ID:

NABTT-0602 CDR0000507451



Start Date:

February 2007

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult gliosarcoma
  • adult giant cell glioblastoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612
Lurleen Wallace Comprehensive Cancer at University of Alabama - BirminghamBirmingham, Alabama  35294