Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00011778
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
2001-02-28
Brief Title:
PS-341 and Radiation to Treat Advanced Cancer of the Head and Neck
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Study of Concomitant Therapy With Proteasome Inhibitor PS-341 and Radiation in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Status:
COMPLETED
Status Verified Date:
2013-02-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will test the safety and effects of the experimental drug PS-341 plus radiation therapy in patients with head and neck cancer PS-341 can slow or halt the growth of cancer cells grown in culture or in mice In addition the drug appears to enhance the effectiveness of radiation treatment
Patients 18 years of age and older with head and neck cancer that cannot be treated adequately with surgery and cannot be cured with standard radiation and chemotherapy may be eligible for this study Patients whose cancer has spread to the brain may not participate
Before treatment begins participants are evaluated with CT or MRI scans of the head neck and chest area to determine the extent of the cancer an electrocardiogram and blood tests and a neurocardiovascular evaluation that includes measuring blood pressure in different body positions and involves injections of phenylephrine and nitroglycerine Some patients may undergo a procedure in which a tube is inserted into the larynx voice box bronchi breathing tubes and esophagus food tube and tissue samples removed This procedure is done under general anesthesia in the operating room
Patients receive radiation treatments Monday through Friday and injections of PS-341 twice a week during the radiation therapy After 3 weeks of treatment PS-341 injections are stopped for 2 weeks Some patients continue to receive radiation treatments during the 2-week break and others do not depending upon when they enter the trial The total duration of radiation treatment varies from 6 to 8 weeks depending on whether the patient received radiation in the region of the head and neck cancer before entering the study
Patients have a blood sample drawn before and after each new PS-341 injection to measure the drug action in the blood and to see how strong and how long the effects on the blood last They are seen in the clinic at least once a week for a history and physical examination A blood sample is collected at each visit to look for toxic effects of PS-341 Near the end of treatment the neurocardiovascular evaluation is repeated and if the results are abnormal it is repeated again 3 months after treatment is completed X-rays or MRI scans are done 12 weeks after radiation therapy has ended and then every few months after that to determine the extent of disease Patients whose tumor is accessible are asked to undergo a biopsy removal of a small piece of tumor tissue on the first and second day after receiving the first PS-341 dose to examine the effect of the drug on the tumor
The PS-341 dose is increased in successive groups of at least 3 patients until the highest dose that can be given safely with radiation is reached Patients who develop severe side effects from the drug temporarily stop taking it to allow the side effects to improve If needed the dose may be decreased Radiation therapy may also be stopped temporarily in patients who develop severe effects on the mouth throat or skin Side effects may be treated with increased fluid by mouth stomach tube or vein anti-nausea or anti-diarrhea medications pain medications and medications to boost red or white cell counts or platelets The drug Florinef may be given to help regulate body fluids and blood pressure
Patients 18 years of age and older with head and neck cancer that cannot be treated adequately with surgery and cannot be cured with standard radiation and chemotherapy may be eligible for this study Patients whose cancer has spread to the brain may not participate
Before treatment begins participants are evaluated with CT or MRI scans of the head neck and chest area to determine the extent of the cancer an electrocardiogram and blood tests and a neurocardiovascular evaluation that includes measuring blood pressure in different body positions and involves injections of phenylephrine and nitroglycerine Some patients may undergo a procedure in which a tube is inserted into the larynx voice box bronchi breathing tubes and esophagus food tube and tissue samples removed This procedure is done under general anesthesia in the operating room
Patients receive radiation treatments Monday through Friday and injections of PS-341 twice a week during the radiation therapy After 3 weeks of treatment PS-341 injections are stopped for 2 weeks Some patients continue to receive radiation treatments during the 2-week break and others do not depending upon when they enter the trial The total duration of radiation treatment varies from 6 to 8 weeks depending on whether the patient received radiation in the region of the head and neck cancer before entering the study
Patients have a blood sample drawn before and after each new PS-341 injection to measure the drug action in the blood and to see how strong and how long the effects on the blood last They are seen in the clinic at least once a week for a history and physical examination A blood sample is collected at each visit to look for toxic effects of PS-341 Near the end of treatment the neurocardiovascular evaluation is repeated and if the results are abnormal it is repeated again 3 months after treatment is completed X-rays or MRI scans are done 12 weeks after radiation therapy has ended and then every few months after that to determine the extent of disease Patients whose tumor is accessible are asked to undergo a biopsy removal of a small piece of tumor tissue on the first and second day after receiving the first PS-341 dose to examine the effect of the drug on the tumor
The PS-341 dose is increased in successive groups of at least 3 patients until the highest dose that can be given safely with radiation is reached Patients who develop severe side effects from the drug temporarily stop taking it to allow the side effects to improve If needed the dose may be decreased Radiation therapy may also be stopped temporarily in patients who develop severe effects on the mouth throat or skin Side effects may be treated with increased fluid by mouth stomach tube or vein anti-nausea or anti-diarrhea medications pain medications and medications to boost red or white cell counts or platelets The drug Florinef may be given to help regulate body fluids and blood pressure
Detailed Description:
Background
The ubiquitin-proteasome pathway regulates the degradation of important regulatory proteins and transcription factors that control the cell cycle and cell death Proteasome inhibition can lead to block of different phases of the cell cycle and block expression of genes that prevent cell death induced by radiation or other cytotoxic therapeutic agents
In preclinical studies proteasome inhibitor PS-341 has demonstrated cytotoxic radiosensitizing and anti-tumor activity against squamous cell carcinomas of the head and neck SCCHN
Objectives
The primary objective of this phase I dose escalation clinical study is to determine the maximum tolerated dose of PS-341 to be given concomitant with radiation in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Secondary objectives include detection of 20S proteasome inhibition cell cycle block apoptosis and inhibition of transcription factor NF-kappaB activation in tumor tissue biopsies following PS-341 and radiation
Eligibility
Persistent or recurrent SCCHN
Eligible for local primary or re-irradiation
ECOG performance less than or equal to 2 life expectancy 3 months
Adequate organ function PLT 100 000microL neutrophils 1500mciroL serum creatinine 15 times the upper limits normal ULN serum bilirubin 15 times the ULN serum transaminases 25 times the ULN
No systemic chemotherapy within the past 4 weeks and recovered from chemotherapy toxicity
6 months since prior radiation
Design
Phase I dose escalation standard 33 statistical design up to 51 subjects
PS-341 will be given in escalating doses of 06 09 and 12 mgm2 in cohorts of 3 or more patients by IV bolus on M Th or T F and radiation will be given in 18 Gy fractions M-F to 60 Gy in previously radiated or 72Gy in previously unirradiated patients
Radiation andor drug will be given in two courses split by a two week rest to allow recovery from combined modality therapy
The ubiquitin-proteasome pathway regulates the degradation of important regulatory proteins and transcription factors that control the cell cycle and cell death Proteasome inhibition can lead to block of different phases of the cell cycle and block expression of genes that prevent cell death induced by radiation or other cytotoxic therapeutic agents
In preclinical studies proteasome inhibitor PS-341 has demonstrated cytotoxic radiosensitizing and anti-tumor activity against squamous cell carcinomas of the head and neck SCCHN
Objectives
The primary objective of this phase I dose escalation clinical study is to determine the maximum tolerated dose of PS-341 to be given concomitant with radiation in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Secondary objectives include detection of 20S proteasome inhibition cell cycle block apoptosis and inhibition of transcription factor NF-kappaB activation in tumor tissue biopsies following PS-341 and radiation
Eligibility
Persistent or recurrent SCCHN
Eligible for local primary or re-irradiation
ECOG performance less than or equal to 2 life expectancy 3 months
Adequate organ function PLT 100 000microL neutrophils 1500mciroL serum creatinine 15 times the upper limits normal ULN serum bilirubin 15 times the ULN serum transaminases 25 times the ULN
No systemic chemotherapy within the past 4 weeks and recovered from chemotherapy toxicity
6 months since prior radiation
Design
Phase I dose escalation standard 33 statistical design up to 51 subjects
PS-341 will be given in escalating doses of 06 09 and 12 mgm2 in cohorts of 3 or more patients by IV bolus on M Th or T F and radiation will be given in 18 Gy fractions M-F to 60 Gy in previously radiated or 72Gy in previously unirradiated patients
Radiation andor drug will be given in two courses split by a two week rest to allow recovery from combined modality therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-C-0104 | None | None | None |