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A Trial of LONSURF in Recurrent/Metastatic Nasopharyngeal Carcinoma

Primary Purpose

Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
TAS-102
Sponsored by
National University Hospital, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Nasopharyngeal Carcinoma focused on measuring TAS102, NPC

Eligibility Criteria

21 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patient

Arm Description

Patients with EBER positive nasopharyngeal carcinoma with recurrent or metastatic disease

Outcomes

Primary Outcome Measures

Disease control rate
As defined by complete response (CR) + partial response (PR) + stable disease (SD) at 12 weeks of assessment using RECIST 1.1.

Secondary Outcome Measures

Progression free survival rate of patients
as defined as the time from initiation of treatment to radiological progression, clinical deterioration or death.
Best objective response rate
as assessed by RECIST 1.1

Full Information

First Posted
September 8, 2020
Last Updated
November 11, 2020
Sponsor
National University Hospital, Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT04627961
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Recruiting
Study Start Date
August 26, 2020 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 To determine the clinical efficacy of TAS-102 in recurrent and metastatic NPC To assess the safety and tolerability of TAS-102 in the study population of R/M NPC To study the pharmacokinetics of TAS-102 in the study population of R/M NPC To study potential predictive biomarkers for clinical benefit from TAS-102

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma
Keywords
TAS102, NPC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Eligible patients who consent to participate will receive oral TAS-102 for days 1-5 and 8-12 of a 28 day cycle.
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patient
Arm Type
Experimental
Arm Description
Patients with EBER positive nasopharyngeal carcinoma with recurrent or metastatic disease
Intervention Type
Drug
Intervention Name(s)
TAS-102
Other Intervention Name(s)
LONSURF
Intervention Description
Eligible patients who consent to participate will receive oral TAS-102 bid for days 1-5 and 8-12 of a 28 day cycle.
Primary Outcome Measure Information:
Title
Disease control rate
Description
As defined by complete response (CR) + partial response (PR) + stable disease (SD) at 12 weeks of assessment using RECIST 1.1.
Time Frame
45 months
Secondary Outcome Measure Information:
Title
Progression free survival rate of patients
Description
as defined as the time from initiation of treatment to radiological progression, clinical deterioration or death.
Time Frame
45 months
Title
Best objective response rate
Description
as assessed by RECIST 1.1
Time Frame
45 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The participant (or legally acceptable representative if applicable) provides written consent for the trial. 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. 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. 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. 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. Willingness to donate blood for translational research studies. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 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 Absolute neutrophil count (ANC) > 1.5x109/L Platelets ≥ 100 x109/L 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 Serum total bilirubin (Tbil) < 1.5 X ULN EXCEPT Patients with Gilbert's Syndrome, who can have Tbil < 3.0 mg/dL AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Coagulation 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 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. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR 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. 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: 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. 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. Has a known history of active TB (Bacillus Tuberculosis). 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. 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. 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. Has an active infection requiring systemic therapy. 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. 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. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boon Cher Goh
Phone
6779 5555
Email
phcgbc@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boon Cher Goh
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boon Cher Goh
Phone
65-6772-4617
Email
Boon_Cher_Goh@nuhs.com.sg

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21319149
Citation
An X, Wang FH, Ding PR, Deng L, Jiang WQ, Zhang L, Shao JY, Li YH. Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy. Cancer. 2011 Aug 15;117(16):3750-7. doi: 10.1002/cncr.25932. Epub 2011 Feb 11.
Results Reference
result
PubMed Identifier
19097774
Citation
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Results Reference
result

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A Trial of LONSURF in Recurrent/Metastatic Nasopharyngeal Carcinoma

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