Clinical trial NCT00637637: External-Beam Radiation Therapy With or Without Indinavir and Ritonavir in Treating Patients With Brain Metastases
Official title: Radiation Therapy in Combination With Indinavir / Ritonavir (Crixivan / Norvir) for the Treatment of Brain Metastases: a Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cancer
Keywords: tumors metastatic to brain
stage IV adenoid cystic carcinoma of the oral cavity
stage IV adrenocortical carcinoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult T-cell leukemia/lymphoma
stage IV anal cancer
stage IV basal cell carcinoma of the lip
stage IV bladder cancer
stage IV borderline ovarian surface epithelial-stromal tumor
stage IV breast cancer
stage IV childhood anaplastic large cell lymphoma
stage IV childhood Hodgkin lymphoma
stage IV childhood large cell lymphoma
stage IV childhood liver cancer
stage IV childhood lymphoblastic lymphoma
stage IV childhood small noncleaved cell lymphoma
stage IV chronic lymphocytic leukemia
stage IV colon cancer
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage IV esophageal cancer
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV follicular thyroid cancer
stage IV gastric cancer
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV hypopharyngeal cancer
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV laryngeal cancer
stage IV lip and oral cavity cancer
stage IV lymphoepithelioma of the nasopharynx
stage IV lymphoepithelioma of the oropharynx
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV mycosis fungoides/Sezary syndrome
stage IV nasopharyngeal cancer
stage IV non-small cell lung cancer
stage IV oropharyngeal cancer
stage IV ovarian epithelial cancer
stage IV pancreatic cancer
stage IV papillary thyroid cancer
stage IV paranasal sinus and nasal cavity cancer
stage IV penile cancer
stage IV prostate cancer
stage IV rectal cancer
stage IV renal cell cancer
stage IV salivary gland cancer
stage IV small lymphocytic lymphoma
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV endometrial carcinoma
stage IV verrucous carcinoma of the larynx
stage IV verrucous carcinoma of the oral cavity
stage IVB vulvar cancer
stage IV Wilms tumor
stage IVB cervical cancer
stage IVB vaginal cancer
metastatic adult malignant fibrous histiocytoma of bone
metastatic childhood malignant fibrous histiocytoma of bone
metastatic gastrointestinal carcinoid tumor
metastatic parathyroid cancer
metastatic pheochromocytoma
metastatic squamous neck cancer with occult primary squamous cell carcinoma
metastatic squamous neck cancer with occult primary
metastatic transitional cell cancer of the renal pelvis and ureter
disseminated neuroblastoma
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific
tongue cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-03-18
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Indinavir and ritonavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether external-beam radiation therapy is more effective with or without indinavir and ritonavir in treating patients with brain metastases.

PURPOSE: This randomized phase II trial is studying external-beam radiation therapy alone to see how well it works compared to external-beam radiation therapy given together with indinavir and ritonavir in treating patients with brain metastases.

Detailed description: OBJECTIVES:

* Compare the efficacy, in terms of time to treatment failure at CNS level and 4-months treatment failure rate, in patients with brain metastases treated with external-beam radiotherapy in combination with indinavir sulfate and ritonavir versus external-beam radiotherapy alone.
* Prospectively investigate the efficacy of a potentially antiangiogenic agent, indinavir sulfate.
* Investigate the antineoplastic activity of indinavir sulfate in combination with ionizing radiation in cancer patients with metastatic disease to the brain.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo radiotherapy to the brain once daily, 5 days a week for 2 weeks (10 doses total). Patients also receive oral indinavir sulfate and oral ritonavir twice daily for 35 days beginning at day 1 of radiotherapy.
* Arm II: Patients undergo radiotherapy to the brain once daily, 5 days a week for 2 weeks (10 doses total).

Patients complete quality of life questionnaires, including QOL-30 and the Mini Mental Status Examination, at baseline, 2 weeks after completion of radiotherapy, and at 1 and 3 months after completion of study treatment.

After completion of study treatment, patients are followed periodically for at least 4 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic cancer with brain metastases

  * Biopsy of brain metastases is not required
* All cancer types allowed, except for the following:

  * Prostatic adenocarcinoma
  * Sarcoma
  * Melanoma
  * Germ cell carcinoma,
  * Small-cell lung cancer
* Measurable disease by MRI of the brain
* Not requiring immediate surgical decompression (may qualify after surgery, if remaining measurable brain lesions)

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2 (corresponds to recursive partitioning analysis groups I or II)
* Life expectancy \> 4 months
* Able to understand the aim of trial and to comply with follow-up
* No HIV seropositivity

PRIOR CONCURRENT THERAPY:

* Prior dexamethasone allowed provided it is tapered before initiation of study radiotherapy
* Not requiring cytotoxic treatment within 3 months after study radiotherapy
* At least 1 week since prior and no concurrent phenytoin

Primary outcomes:
measure: Time to treatment failure in the brain (TTF) as determined by the radiological response rate
measure: Overall survival (OS)
measure: Radiological volumetric response to treatment
measure: Local intracranial disease progression at 4 months
measure: Progression-free survival at 6 months
Secondary outcomes:
measure: Improvement of symptoms
measure: Time to symptom relapse or symptom progression
measure: Duration of use of steroids
measure: Duration of use of anticonvulsive drugs
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lugano
country: Switzerland
facility: Oncology Institute of Southern Switzerland - Lugano
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Oncology Institute of Southern Switzerland
name: Ilja Ciernik, MD
role: PRINCIPAL_INVESTIGATOR
References: