Brief Title
A Trial of LONSURF in Recurrent/Metastatic Nasopharyngeal Carcinoma
Official Title
A Phase 2 Trial of TAS 102 in Recurrent/Metastatic Nasopharyngeal Carcinoma
Brief Summary
This is a single-arm, non-randomised study including patients with EBER positive
nasopharyngeal carcinoma with recurrent or metastatic disease not amenable to curative
treatment, who have received at least 1 regimen of platinum containing chemotherapy.
Detailed Description
HYPOTHESIS
Given the favourable activity of fluoropyrimidines (5Fluorouracil) which inhibit thymidylate
synthase (TS) in nasopharyngeal carcinoma, the investigators hypothesized that TAS-102 may
demonstrate efficacy in NPC through targeting TS as well as an additional mechanism of
incorporating trifluridine triphosphate into DNA.
OBJECTIVES OF TRIAL
1. To determine the clinical efficacy of TAS-102 in recurrent and metastatic NPC
2. To assess the safety and tolerability of TAS-102 in the study population of R/M NPC
3. To study the pharmacokinetics of TAS-102 in the study population of R/M NPC
4. To study potential predictive biomarkers for clinical benefit from TAS-102
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Disease control rate
Secondary Outcome
Progression free survival rate of patients
Condition
Metastatic Nasopharyngeal Carcinoma
Intervention
TAS-102
Study Arms / Comparison Groups
Patient
Description: Patients with EBER positive nasopharyngeal carcinoma with recurrent or metastatic disease
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
33
Start Date
August 26, 2020
Completion Date
October 2024
Primary Completion Date
October 2024
Eligibility Criteria
Inclusion Criteria:
1. The participant (or legally acceptable representative if applicable) provides written
consent for the trial.
2. Participants who are at least 21 years of age on the day of signing informed consent
with histologically or cytologically confirmed diagnosis of non-keratinizing
nasopharyngeal carcinoma (NPC) that has recurred at loco regional and/or distant sites
will be enrolled in this study.
3. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.
4. Have EBV-positive NPC by EBV-encoded small RNA in situ hybridization (EBER in situ
hybridization [ISH]) assay. If EBV-positive status has been previously determined by
EBER ISH assay, then no re-testing is required.
Note: If EBV status by EBER ISH assay has not been previously determined, tumor tissue
from archival tissue may be submitted for EBV determination.
5. Received one or more lines of chemotherapy, which must include prior treatment with a
platinum agent and must not be amenable to potentially curative radiotherapy or
surgery.
6. Willingness to donate blood for translational research studies.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Have an adequate organ function as defined in the following table (Table 1). Specimens
must be collected within 10 days prior to the start of study treatment.
Table 1 Adequate Organ Function Laboratory Values System Laboratory Value
- Hematological
1. Absolute neutrophil count (ANC) > 1.5x109/L
2. Platelets ≥ 100 x109/L
3. Hemoglobin ≥ 8.0 g/dL a
- Renal
a) Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 30
mL/min for participants with creatinine levels > 1.5X ULN
- Hepatic
1. Serum total bilirubin (Tbil) < 1.5 X ULN EXCEPT Patients with Gilbert's
Syndrome, who can have Tbil < 3.0 mg/dL
2. AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
- Coagulation
1. International Normalized Ratio (INR) OR prothrombin time (PT) ≤ 1.5X ULN
unless participant is receiving anticoagulant therapy as long as PT or aPTT
is within therapeutic range of intended use of anticoagulants
2. Activated partial thromboplastin time (aPTT) ≤ 1.5X ULN unless participant
is receiving anticoagulant therapy as long as PT or aPTT is within
therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine
aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate
aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular
filtration rate; ULN=upper limit of normal.
9. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 120 days after the last dose of study medication.
10. A male participant must agree to use a contraception during the treatment period and
for at least 120 days after the last dose of study treatment and refrain from donating
sperm during this period.
Exclusion Criteria:
1. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to randomization.
Note: Participants must have recovered from all AEs to previous therapies to ≤ Grade 1
or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
Note: If participants received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting study
treatment.
2. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to first dose of
study treatment.
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
3. Has a known history of active TB (Bacillus Tuberculosis).
4. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
5. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g.
breast or cervical carcinoma in situ) that have undergone potentially curative therapy
are not excluded.
6. Has known brain metastases or leptomeningeal metastases, whether treated or untreated.
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.
7. Has an active infection requiring systemic therapy.
8. Has 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.
9. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
10. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
11. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
12. A WOCBP who has a positive urine pregnancy test within 72 hours prior to
randomization/allocation (see Appendix 3). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.
Note: In the event that 72 hours have elapsed between the screening pregnancy test and the
first dose of study treatment, another pregnancy test (urine or serum) must be performed
and must be negative in order for subject to start receiving study medication.
Gender
All
Ages
21 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Boon Cher Goh, 6779 5555, [email protected]
Location Countries
Singapore
Location Countries
Singapore
Administrative Informations
NCT ID
NCT04627961
Organization ID
NP01/05/19
Responsible Party
Sponsor
Study Sponsor
National University Hospital, Singapore
Study Sponsor
Boon Cher Goh, Principal Investigator, National University Hospital, Singapore
Verification Date
November 2020