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Nasopharyngeal CarcinomaPhase 2NCT02605967

Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

A Phase 2 study testing Spartalizumab and Investigator choice of chemotherapy in people with Nasopharyngeal Carcinoma, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nasopharyngeal Carcinoma
What is being tested?
Spartalizumab and Investigator choice of chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
18 sitesin 7 countries
Study dates
20 Apr 2016to 19 Feb 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
  • Must be resistant to platinum-based chemotherapy (defined as progression on or after platinum-based chemotherapy given in the recurrent/metastatic setting).
  • May have received at least 1 prior therapy for recurrent or metastatic disease, up to 2 prior systemic therapies.
  • An archival tumor specimen or newly obtained tumor sample may be submitted at screening/baseline (a fresh tumor sample is preferred), unless agreed differently between Novartis and the Investigator.
  • At least 1 measurable lesion (as per RECIST v1.1) progressing or new since last anti-tumor therapy.
  • Prior treated brain or meningeal metastases must be without MRI evidence of progression for at least 8 weeks and off systemic steroids for at least 2 weeks prior to screening/baseline.
  • Patient must be willing to undergo testing for human immunodeficiency virus (HIV) if not tested within the past 6 months. If HIV+ positive, patient will be eligible if: his/ her CD4+ count ≥ 300/μL; his/her viral load is undetectable; he/she is currently receiving highly active antiretroviral therapy (HAART).

Who cannot join

  • History of severe hypersensitivity reactions to other mAbs
  • Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators.
  • Active HBV or HCV infections requiring therapy.
  • Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.
  • Patients receiving systemic treatment with any immunosuppressive medication.
  • Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.

Trial locations and contacts

18 sites in 7 countries.

18 sites in 7 countries

United States4 sites
  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Northwest Georgia Oncology Center NWGA Onc - Carrollton

    Marietta, Georgia, 30060

  • NYU Laura and Isaac Perlmutter Cancer Center Laura & Isaac Perlmutter Ctr

    New York, New York, 10016

Other trials in United States

Taiwan4 sites
  • Novartis Investigative Site

    Kaohsiung City, 83301

  • Novartis Investigative Site

    Tainan, Taiwan ROC, 70403

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Hong Kong3 sites
  • Novartis Investigative Site

    Hong Kong

  • Novartis Investigative Site

    Kowloon

  • Novartis Investigative Site

    Tuenmen

Other trials in Hong Kong

Thailand3 sites
  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Chiang Mai, 50200

  • Novartis Investigative Site

    Songkhla, Hat Yai, 90110

Other trials in Thailand

France2 sites
  • Novartis Investigative Site

    Nice, Alpes Maritimes, 06189

  • Novartis Investigative Site

    Villejuif, Villejuif, 94800

Other trials in France

China1 site
  • Novartis Investigative Site

    Guangzhou, 510060

Other trials in China

Singapore1 site
  • Novartis Investigative Site

    Singapore, 169610

Other trials in Singapore

About this study

Official title: A Phase II, Open-label, Randomized Controlled Study of PDR001 in Patients With Moderately Differentiated/Undifferentiated Locally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma Who Progressed on Standard Treatment

The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced nasopharyngeal carcinoma (NPC).

By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, PDR001 leads to the activation of a T-cell mediated antitumor immune response.

Read the detailed description

This was an open-label, multi-center, randomized, and controlled Phase II study to evaluate the efficacy and safety of spartalizumab versus investigator's choice of treatment in subjects with moderately differentiated/undifferentiated locally advanced recurrent or metastatic NPC who progressed on or after first-line treatment.

Participants who met the inclusion/exclusion criteria were randomized in a 2:1 ratio to either investigational arm (spartalizumab) or control arm (commonly used chemotherapy as per investigator's choice). Participants treated with spartalizumab could continue treatment until confirmed progressive disease as per immune-related response criteria (irRC). Participants in the chemotherapy arm were allowed to crossover to spartalizumab if they had radiological progression as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) documented by an independent central review and the Investigator believed this was the best treatment option for the patient.

Being tested
Spartalizumab, Investigator choice of chemotherapy
Keywords
PDR001, nasopharyngeal cancer, moderately differentiated/undifferentiated, locally advanced, recurrent or metastatic NPC, after first- line platinum-based therapy
Medical subject headings
Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms, Disorders of Sex Development, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SpartalizumabDrug

    Also called PDR001

    Spartalizumab was administered via intravenous infusion at a dose of 400 mg every 4 weeks (Q4W). Spartalizumab is a humanized anti-PD-1 IgG4 antibody which blocks the binding of PD1 to its ligands PD-L1 and PD-L2.

  • Investigator choice of chemotherapyDrug

    Commonly used chemotherapy as per investigator's choice. The dose and route of administration was the one described in each drug's label.

Study groups in NCT02605967
Study groupRoleWhat they receive
Spartalizumab 400 mg Q4WExperimentalanti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
Receives: Drug: Spartalizumab
ChemotherapyActive comparatorcommonly used chemotherapy as per investigator's choice
Receives: Drug: Investigator choice of chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death

    PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

    Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Number of participants in each category (progression, death, censored) is reported in this record.

    Measured: From randomization up to maximum 3.3 years

  2. Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Median PFS

    PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

    Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

    Measured: From randomization up to maximum 3.3 years

Secondary outcomes (18)
  1. Overall Survival (OS)

    Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient is not known to have died, survival is censored at the date of last known date the patient was alive.

    Measured: From randomization up to maximum 4.8 years.

  2. Overall Response Rate (ORR) as Per RECIST v 1.1

    ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). Tumor response was based on central review of overall lesion response according to RECIST 1.1.

    For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: From randomization up to maximum 3.3 years

  3. Duration of Response (DOR) as Per RECIST v 1.1

    DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR) based on central review of overall lesion response according to RECIST 1.1. DOR is defined as the time between the date of first documented response (confirmed CR or confirmed PR) and the date of first documented disease progression or death due to underlying cancer. If a patient not had an event, duration was censored at the date of last adequate tumor assessment.

    Measured: From randomization up to maximum 3.3 years

  4. Time to Progression (TTP) as Per RECIST v 1.1

    TTP is defined as time from date of randomization to the date of event defined as the first documented progression or death due to underlying cancer. If a subject did not had an event, TTP was censored at the date of last adequate tumor assessment.

    Tumor response was based on central review of tumor scan and the assessment criteria was RECIST v1.1. Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

    Measured: From randomization up to maximum 3.3 years

  5. Immune-related Progression-free Survival (irPFS) as Per irRC

    irPFS is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

    Tumor response was based on central review of tumor scan and the assessment criteria was immune-related Response Criteria (irRC). Immune-related progressive disease is at least a 20% increase in the sum of diameters of all measured target lesions including new measurable lesions.

    Measured: From randomization up to maximum 3.3 years

  6. Maximum Observed Serum Concentration (Cmax) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  7. Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  8. Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. The duration of the dosing interval (tau) was 28 days.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  9. Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. The extrapolation of AUC to infinity could be calculated if the percentage of area extrapolated was less than 20% and the regression analysis of the terminal serum elimination phase met a pre-defined criteria of goodness of fit.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  10. Accumulation Ratio (Racc) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Racc was calculated as the ratio between AUCtau Cycle 3 and AUCtau Cycle 1.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  11. Terminal Elimination Half-life (T1/2) of Spartalizumab

    Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant.

    Measured: pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.

  12. Number of Participants With Anti-spartalizumab Antibodies

    Validated immunoassays were used for screening and confirmation of the presence of anti-spartalizumab antibodies (ADA, anti-drug antibodies) in serum. Number of participants with each ADA status is reported in this record.

    Measured: Baseline (pre-dose on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 655 days).

  13. PD-L1 Percent Positive Tumor

    The expression of programmed cell death-ligand 1 (PD-L1) was measured in tumor samples by immunohistochemical methods. This record summarizes the PD-L1 positivity percentage in tumor samples.

    Measured: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.

  14. Percent Marker Area for CD8 Expression in Tumor Samples

    The expression of CD8 was measured in tumor samples by immunohistochemical methods. This record summarizes the percent marker area for CD8 expression in tumor samples.

    Measured: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.

  15. TIL Count in Tumor Samples

    The count of tumor-infiltrating lymphocytes (TILs) was measured in baseline (screening) and post-baseline paired tumor samples by immunohistochemical methods. This record summarizes the TIL count in tumor samples.

    Measured: Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.

  16. Fold Change From Baseline in IFN-gamma Levels in Plasma

    The levels of interferon-gamma (IFN-gamma) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in IFN-gamma levels in plasma.

    Measured: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.

  17. Fold Change From Baseline in IL-6 Levels in Plasma

    The levels of interleukin-6 (IL-6) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in IL-6 levels in plasma.

    Measured: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.

  18. Fold Change From Baseline in TNF-alfa Levels in Plasma

    The levels of tumor necrosis factor-alpha (TNF-alfa) were measured in plasma samples by immunoassay methods. This record summarizes the fold change from baseline in TNF-alfa levels in plasma.

    Measured: Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2015 (estimated)
  2. Study start20 Apr 2016
  3. Primary completion5 Nov 2019
  4. Study completion19 Feb 2021

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
122 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02605967
Sponsor's protocol ID
CPDR001X2201
Other IDs
2015-000454-38, 2015
Status last verified
Jan 2022
First submitted
15 Oct 2015
Last updated
10 Feb 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Even C, Wang HM, Li SH, Ngan RK, Dechaphunkul A, Zhang L, Yen CJ, Chan PC, Chakrabandhu S, Ma BBY, Tanasanvimon S, Lee VHF, Lou PJ, Li Z, Spira AI, Sukari A, Guigay J, McCune S, Gonzalez-Maffe J, Szpakowski S, Yao Y, Liang H, Mataraza J, Sechaud R, Manenti L, Lim DW. Phase II, Randomized Study of Spartalizumab (PDR001), an Anti-PD-1 Antibody, versus Chemotherapy in Patients with Recurrent/Metastatic Nasopharyngeal Cancer. Clin Cancer Res. 2021 Dec 1;27(23):6413-6423. doi: 10.1158/1078-0432.CCR-21-0822. Epub 2021 Aug 25.

    PubMed 34433653

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Spartalizumab and Investigator choice of chemotherapy in people with Nasopharyngeal Carcinoma, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

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 7 inclusion and 6 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 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Taiwan, Hong Kong, Thailand, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 12 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death (time frame: From randomization up to maximum 3.3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02605967, which also lists 1 linked publication.

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 10 Feb 2022.

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