Recurrent Nasopharyngeal Undifferentiated CarcinomaPhase 2NCT02794077
Cyclophosphamide for Nasopharyngeal Carcinoma
A Phase 2 study testing Cyclophosphamide in people with Recurrent Nasopharyngeal Undifferentiated Carcinoma and Stage IV Nasopharyngeal Undifferentiated Carcinoma, run by The University of Hong Kong.
Trial summary
There is no standard third-line systemic treatment for inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). We investigated the efficacy and safety of metronomic oral cyclophosphamide as third-line treatment or beyond. Read more about this study
- Who is it for?
- Ages 15 to 80 years
- Conditions the study is for
- Recurrent Nasopharyngeal Undifferentiated Carcinoma, Stage IV Nasopharyngeal Undifferentiated Carcinoma
- What is being tested?
- Cyclophosphamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- No sites listed yet
- Study dates
- Jan 2008to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Inoperable locoregionally advanced recurrent NPC of undifferentiated type beyond curative surgical resection or second and subsequent courses of radical radiotherapy or metastatic disease who all had received at least 2 lines palliative systemic chemotherapy
- Adequate hematological function defined as absolute neutrophil count ≥1.5 × 10^9/l; hemoglobin ≥9.0 g/dl and platelet ≥100 × 10^9/l
- Adequate renal function defined as serum creatinine ≤1.5 × upper normal limit
- Adequate hepatic function defined as serum bilirubin ≤1.5 × upper normal limit; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper normal limit for patients without liver metastases or ≤5 × upper normal limit for those with liver metastases
- Measurable disease according to the RECIST criteria (version 1.1), for the evaluation of measurable disease
Who cannot join
- Eastern Cooperative Oncology Group (ECOG) performance status 3 or above
- Known brain metastases or leptomeningeal metastases; Note: symptomatic, and/or if they require immunosuppressive doses of corticosteroids (e.g. > 10 mg/day prednisone or equivalents) for at least 2 weeks prior to study drug administration; patients with treated brain metastases who are deemed clinically stable and without radiological progression on positron emission tomography (PET), MRI or computed tomography (CT) scan performed =< 8 weeks of study entry, are not excluded; Note: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa (e) are not regarded as brain metastases and are not excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide
- History of severe hypersensitivity reaction to any monoclonal antibody
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Any of the following:
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- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception Note: breastfeeding should be discontinued if the mother is treated with cyclophosphamide; women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; they must adhere to contraception for a period of 31 weeks after the last dose of cyclophosphamide
- For patients with unknown human immunodeficiency virus (HIV) status at the time of enrollment, HIV serology must be tested during screening; patients who are tested positive for HIV could be included if there is an adequate cluster of differentiation 4 (CD4) count (> 350/ul) on a stable regimen of highly active anti-retroviral therapy (HAART) with no detectable or minimal viral burden, and no active infections
- Those who cannot provide written informed consent
About this study
Official title: Metronomic Oral Cyclosphosphamide as Third-line Systemic Treatment or Beyond in Patients With Inoperable Locoregionally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma
There is no standard third-line systemic treatment for inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). We investigated the efficacy and safety of metronomic oral cyclophosphamide as third-line treatment or beyond.
Read the detailed description
NPC is endemic in Southern China including Hong Kong. Despite aggressive definitive chemoradiotherapy for locoregionally advanced disease, still about 30% develop relapse locoregionally or distally. Salvage or second-course radical radiotherapy with or without chemotherapy may achieve durable disease control for locoregionally advanced recurrent disease. However for those who had received 2 courses of radical radiotherapy or those with distant metastases, systemic chemotherapy would be the only drug of choice. Platinum-based doublet chemotherapy including cisplatin + 5-fluorouracil, capecitabine, gemcitabine or taxane is considered the standard first-line treatment. For second-line treatment, whether platinum-based chemotherapy was given previously is a consideration. Re-challenge with cisplatin and 5-fluorouracil can be considered in patients who enjoyed a good initial response to the same regimen with an intervening disease-free period of more than 1 year.However so far there has been no recognized standard third-line systemic treatment. Metronomic oral chemotherapy may provide an ideal choice patients treated in this setting by shifting the targets from tumor cells to tumor vasculature so as to reduce the chance of drug resistance as well as offering a relatively low toxicity profile to them who have been significantly jeopardized by the long-term complications brought prior courses of radiation therapy, surgery and chemotherapy.
In view of the above, we investigated metronomic open-label oral cyclophosphamide as third-line treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic NPC who had failed at least 2 lines of prior systemic chemotherapy.
- Conditions
- Recurrent Nasopharyngeal Undifferentiated Carcinoma, Stage IV Nasopharyngeal Undifferentiated Carcinoma
- Being tested
- Cyclophosphamide
- Keywords
- Nasopharyngeal undifferentiated carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Endoxan
Patient receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progressive or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide | Experimental | Patients receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Interval between the date of commencement of cyclophosphamide to the date of radiologically confirmed progressive disease or death, whichever comes earlier.
Measured: 12 months
Secondary outcomes (4)
Objective response rate
The percentage of patients who demonstrate complete response or partial response after study medication as assessed by RECIST 1.1
Measured: 12 months
Disease control rate
The percentage of patients who demonstrate complete response, partial response or stable disease after study medication as assessed by RECIST 1.1
Measured: 12 months
Number of participants with treatment-related adverse events as assessed by CTCAE version 4.0
All treatment-related adverse events as assessed by CTCAE version 4.0 will be recorded
Measured: 12 months
Overall survival
Time interval between the date of commencement of cyclophosphamide to the date of death
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2016 (estimated)
- Study startJan 2008
- Primary completionDec 2015
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Nasopharyngeal Undifferentiated CarcinomaStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Victor H.F. Lee, The University of Hong Kong
- Investigators
- Victor Lee, MD, Principal investigator, Department of Clinical Oncology, The University of Hong Kong, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02794077
- Sponsor's protocol ID
- Cyclophosphamide
- Status last verified
- Sep 2019
- First submitted
- 30 May 2016
- Last updated
- 2 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: There is no plan for to make individual participant data available.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metronomic Oral Cyclosphosphamide as Third-line Systemic Treatment or Beyond in Patients With Inoperable Locoregionally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT02794077
- Acronym / sponsor ID
- Cyclophosphamide
- Conditions
- Recurrent Nasopharyngeal Undifferentiated Carcinoma, Stage IV Nasopharyngeal Undifferentiated Carcinoma
- Keywords
- Nasopharyngeal undifferentiated carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 8 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is no standard third-line systemic treatment for inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). We investigated the efficacy and safety of metronomic oral cyclophosphamide as third-line treatment or beyond.
Detailed description
NPC is endemic in Southern China including Hong Kong. Despite aggressive definitive chemoradiotherapy for locoregionally advanced disease, still about 30% develop relapse locoregionally or distally. Salvage or second-course radical radiotherapy with or without chemotherapy may achieve durable disease control for locoregionally advanced recurrent disease. However for those who had received 2 courses of radical radiotherapy or those with distant metastases, systemic chemotherapy would be the only drug of choice. Platinum-based doublet chemotherapy including cisplatin + 5-fluorouracil, capecitabine, gemcitabine or taxane is considered the standard first-line treatment. For second-line treatment, whether platinum-based chemotherapy was given previously is a consideration. Re-challenge with cisplatin and 5-fluorouracil can be considered in patients who enjoyed a good initial response to the same regimen with an intervening disease-free period of more than 1 year.However so far there has been no recognized standard third-line systemic treatment. Metronomic oral chemotherapy may provide an ideal choice patients treated in this setting by shifting the targets from tumor cells to tumor vasculature so as to reduce the chance of drug resistance as well as offering a relatively low toxicity profile to them who have been significantly jeopardized by the long-term complications brought prior courses of radiation therapy, surgery and chemotherapy.
In view of the above, we investigated metronomic open-label oral cyclophosphamide as third-line treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic NPC who had failed at least 2 lines of prior systemic chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide | Experimental | Drug: CyclophosphamidePatients receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 15 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Inoperable locoregionally advanced recurrent NPC of undifferentiated type beyond curative surgical resection or second and subsequent courses of radical radiotherapy or metastatic disease who all had received at least 2 lines palliative systemic chemotherapy
- Adequate hematological function defined as absolute neutrophil count ≥1.5 × 10^9/l; hemoglobin ≥9.0 g/dl and platelet ≥100 × 10^9/l
- Adequate renal function defined as serum creatinine ≤1.5 × upper normal limit
- Adequate hepatic function defined as serum bilirubin ≤1.5 × upper normal limit; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper normal limit for patients without liver metastases or ≤5 × upper normal limit for those with liver metastases
- Measurable disease according to the RECIST criteria (version 1.1), for the evaluation of measurable disease
Key exclusion criteria (11 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status 3 or above
- Known brain metastases or leptomeningeal metastases; Note: symptomatic, and/or if they require immunosuppressive doses of corticosteroids (e.g. > 10 mg/day prednisone or equivalents) for at least 2 weeks prior to study drug administration; patients with treated brain metastases who are deemed clinically stable and without radiological progression on positron emission tomography (PET), MRI or computed tomography (CT) scan performed =< 8 weeks of study entry, are not excluded; Note: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa (e) are not regarded as brain metastases and are not excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide
- History of severe hypersensitivity reaction to any monoclonal antibody
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideAlso: EndoxanPatient receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progressive or unacceptable toxicity. | Drug | Cyclophosphamide |
Primary outcome
Progression-free survival
Time frame: 12 months
Interval between the date of commencement of cyclophosphamide to the date of radiologically confirmed progressive disease or death, whichever comes earlier.
4 secondary outcomes
Objective response rate
Time frame: 12 months
Disease control rate
Time frame: 12 months
Number of participants with treatment-related adverse events as assessed by CTCAE version 4.0
Time frame: 12 months
Overall survival
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2019.
- Individual participant dataSharing planned: No. There is no plan for to make individual participant data available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victor Lee, MD principal investigator
Department of Clinical Oncology, The University of Hong Kong, Hong Kong
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide in people with Recurrent Nasopharyngeal Undifferentiated Carcinoma and Stage IV Nasopharyngeal Undifferentiated Carcinoma, run by The University of Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2019.