Temozolomide in Treating Patients With Invasive Pituitary Tumors

NCT00601289 | Withdrawn Phase 2 DMC

• 2 other identifiers: CDR000057753407-05-077-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with invasive pituitary tumors.

Conditions

Brain and Central Nervous System Tumors

Keywords

pituitary chromophobe adenoma; recurrent pituitary tumor; ACTH-producing pituitary tumor; growth hormone-producing pituitary tumor; prolactin-producing pituitary tumor; pituitary basophilic adenoma; pituitary eosinophilic adenoma; prolactin secreting adenoma; nonfunctioning pituitary tumor

Outcome Measures

Primary Outcomes (3)

• Change from baseline of pituitary tumor control as assessed by MRI at 3, 6, 9, and 12 months

  1 year

• Change in Tumor response rate (complete response or partial response) from baseline as assessed by RECIST criteria at 3, 6, 9, and 12 months

  1 year

• Rebound tumor growth as assessed by MRI at 6 months after completion of treatment

  6 months

Secondary Outcomes (4)

• Biochemical control as assessed by measurement of hormones secreted in excess by the pituitary tumor at baseline, at 3, 6, 9, and 12 months during treatment, and then at 2 months after completion of treatment

  14 months

• Pituitary function as assessed by standard pituitary function tests at baseline and at 6 months and 12 months

  1 year

• Safety and tolerability of temozolomide as assessed by NCI CTC v2.0 at screening, baseline, and then monthly until study completion

  1 year

• Overall quality of life as assessed by Karnofsky performance status questionnaire periodically during study

  1 year

Interventions

temozolomide DRUG

DNA methylation analysis GENETIC

microarray analysis GENETIC

protein expression analysis GENETIC

proteomic profiling GENETIC

laboratory biomarker analysis OTHER

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Clinically demonstrable invasive pituitary macroadenoma, including any of the following subtypes: * Growth hormone-secreting * Prolactin-secreting * Adrenocorticotrophic hormone-secreting * Non-secreting * Must have biochemical evidence of any of the following: * Acromegaly as measured by serum insulin-like growth factor-1 (IGF-1) * Prolactinoma as measured by serum prolactin (PRL) * Cushing's disease as measured by 24-hour urinary-free cortisol * Inadequate tumor control, defined as a visible pituitary tumor ≥ 1 cm in maximal diameter encasing the carotid arteries, and/or invading into the cavernous sinuses, and/or abutting/invading the optic chiasma as demonstrated by MRI scan with or without contrast * Previously assessed by radiosurgery and meets ≥ 1 of the following criteria: * Not a suitable candidate for radiotherapy (e.g., tumor abutting and/or invading the optic chiasm) * Declined radiotherapy (in light of side effects or personal choice) * Has not exhibited tumor shrinkage or tumor continues to grow ≥ 1 year after completion of radiotherapy * Must have a normal visual field evaluation by Goldman perimetry * No visual field abnormalities * Hypopituitarism allowed as evidenced by any or all of the following: * Subnormal growth hormone response to arginine/growth hormone-releasing hormone testing (normal response is an increase of \> 4 ng/mL) * Low age- and sex-matched IGF-1 levels * Low thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels * Low estradiol levels * Low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in postmenopausal female patients OR low testosterone, LH, and FSH levels in male patients * Serum cortisol \< 3 ng/mL (at 8 am) * Patients diagnosed with hypopituitarism (except for post-menopausal females) are required to initiate hormone replacement therapy for the 12-month duration of the study and to discontinue hormone replacement therapy at the end of 12 months to re-evaluate hypopituitarism PATIENT CHARACTERISTICS: * Able to undergo a pituitary MRI scan * No clinically significant renal, hematologic, or hepatic abnormalities * No prior or concurrent medical condition that may interfere with the conduct of the study or the evaluation of its results, in the opinion of the Investigator or the Data Safety Monitoring Board compliance officer * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception for ≥ 2 months prior to, during, and for 1 month after completion of study therapy * No history of immunocompromise, including known HIV positivity as measured by enzyme linked immunosorbent assay (ELISA) and western blot * No alcohol or drug abuse within the past 6 months * No blood donation within the past 2 months * No history of noncompliance to medical regimens, potential unreliability, or inability to complete the entire study * No other active malignant disease within the past 5 years, except basal cell carcinoma or carcinoma in situ of the cervix * No active or suspected acute or chronic uncontrolled infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior pituitary surgery allowed provided the surgery failed to induce complete tumor response and the patient is deemed unsuitable for further pituitary surgeries * At least 3 months since prior pituitary surgery * More than 1 month since prior unlicensed drugs or participation in a clinical trial with an investigational drug * No concurrent pituitary surgery or pituitary radiotherapy * No other concurrent therapy to reduce pituitary tumor size

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

MeSH Terms

Conditions

Central Nervous System Neoplasms; Adenoma, Chromophobe; Pituitary Neoplasms; Growth Hormone-Secreting Pituitary Adenoma; Adenoma, Basophil; Adenoma, Acidophil; Prolactinoma

Interventions

Temozolomide; DNA Methylation; Microarray Analysis

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Microchip Analytical Procedures; Investigative Techniques

Study Officials

• Anthony Heaney, MD

  Jonsson Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: January 28, 2008
• Study Start: December 1, 2009
• Primary Completion: October 1, 2010
• Last Updated: July 31, 2020

Record last verified: 2012-07