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Recurrent/Metastatic Head and Neck Squamous Cell CarcinomaPhase 2PIPERNCT05286619

A Study of Pembrolizumab (MK-3475) Plus Platinum and Gemcitabine as First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (PIPER)

A Phase 2 study testing Pembrolizumab, Cisplatin and Carboplatin in people with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, run by University of Malaya at 1 site in Malaysia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is an open-label, single-arm, Phase 2 study of pembrolizumab plus platinum and gemcitabine (PG) in subjects with recurrent or metastatic head and neck cancer squamous cell carcinoma (R/M HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Cisplatin and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
1 siteMalaysia
Study dates
22 Sep 2022to Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies will be enrolled in this study:
  • Subject may not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed.
  • The eligible primary tumour locations are oropharynx, oral cavity, hypopharynx, and larynx.
  • Subject may not have a primary tumour location site of nasopharynx (any histology).
  • A male participant must agree to use a contraception as detailed in Appendix 3: Contraceptive Guidance and Pregnancy Testing of this protocol starting with the first dose of study treatment through the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant (see Appendix 3: Contraceptive Guidance and Pregnancy Testing), not breastfeeding, and at least one of the following conditions applies:
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  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 3: Contraceptive Guidance and Pregnancy Testing OR
  • A WOCBP who agrees to follow the contraceptive guidance in Appendix 3: Contraceptive Guidance and Pregnancy Testingduring the treatment period and for at least 180 days after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) willing and able to provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
  • 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.
  • Archival or fresh tumor tissues must be available for evaluating relevant biomarkers. Newly obtained core needle or excisional biopsy of a tumor lesion not previously irradiated is preferred to archived tissue. If newly obtained samples cannot be obtained due to inaccessibility or patient safety concern, submission of paraffin block or formalin-fixed, paraffin embedded (FFPE) slides of up to 3 years prior to trial enrolment are acceptable (15 unstained slides of 5 microns in thickness). Refer to Section 6.1.5 for complete information on the tissue sample collection.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
  • Have adequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days prior to the start of study intervention.
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelets ≥100 000/µL
  • Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
  • Creatinine ≤1.5 × ULN
  • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Who cannot join

  • Has disease that is suitable for local therapy administered with curative intent.
  • Has progressive disease within six months of completion of curatively intended treatment for locoregionally advanced HNSCC.
  • Patient with an expected life expectancy of less than 3 months.
  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment allocation (see Appendix 4). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to start of study treatment.
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  • Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
  • Has received prior radiotherapy within 2 weeks of start of study intervention. 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 received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
  • 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 the first dose of study intervention.
  • 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 diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant 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 study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Wan Zamaniah Wan Ishak, MBBS, MD contact

0379492120 ext. 2120

wzamaniah@ummc.edu.my

Suganiya Rama Rao contact

0379492120 ext. 2120

suganiya@ummc.edu.my

Malaysia1 site, 1 recruiting

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

    Suganiya Rama Rao, 0379492120, suganiya@ummc.edu.my

    Wan Zamaniah Wan Ishak, Associate professor

    Recruiting

Other trials in Malaysia

About this study

This is an open-label, single-arm, Phase 2 study of pembrolizumab plus platinum and gemcitabine (PG) in subjects with recurrent or metastatic head and neck cancer squamous cell carcinoma (R/M HNSCC). Evaluable 63 subjects with R/M HNSCC will be enrolled for examination of the efficacy and safety of the combination of pembrolizumab (200 mg IV on Day 1 of each 3-week cycle, up to 35 cycles) in combination with platinum (either cisplatin at 35 mg/m2 IV using a split-dose regimen on Day 1 and Day 8 or carboplatin at AUC 5 IV on Day 1 of each 3-week cycle, up to 6 cycles) and gemcitabine at 1250 mg/m2 IV on Day 1 and 8 of each 3-week cycle, for up to 6 cycles as first-line treatment. This study will be conducted in conformance with Good Clinical Practices. Specific procedures to be performed during the trial, as well as their prescribed timelines and associated visit windows, are outlined in the protocol.

Read the detailed description

This is an open label, single arm, Phase 2 study of pembrolizumab plus platinum and gemcitabine (PG) in subjects with recurrent or metastatic head and neck cancer squamous cell carcinoma (R/M HNSCC) to be conducted in conformance with Good Clinical Practices. Evaluable 63 subjects with R/M HNSCC will be enrolled for examination of the efficacy and safety of the combination of pembrolizumab with PG as first line treatment.

The purpose of the study is to determine Pembrolizumab in combination with platinum and gemcitabine chemotherapies would be comparable with or better than the combination of pembrolizumab with platinum plus 5-FU chemotherapies, in terms of objective response rate(ORR), overall survival (OS) and safety as first-line treatment in R/M HNSCC.

All subjects will be given pembrolizumab (200 mg IV on Day 1 of each 3-week cycle, up to 35 cycles) in combination with platinum (either cisplatin at 35 mg/m2 IV using a split dose regimen on Day 1 and Day 8 or carboplatin at AUC 5 IV on Day 1 of each 3-week cycle, up to 6 cycles) and gemcitabine at 1250 mg/m2 IV on Day 1 and 8 of each 3-week cycle, for up to 6 cycles. Disease status will be followed by imaging studies at 6 weekly intervals (±7 days) during the first year, and every 9 weeks (±7 days) after the first year, until disease progression, withdrawal of consent, death or end of study. RECIST 1.1 will be used as the primary efficacy endpoint of response rate. Safety will be monitored according to the National Cancer Institute CTCAE Version 5.0.

Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the protocol under section Schedule of Activities (SoA).

Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

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

  • PembrolizumabDrug

    Pembrolizumab 200mg will be administered on Day 1 every 3 weeks for up to 24months

  • CisplatinDrug

    Cisplatin at 35 mg/m2 IV using a split dose regimen on Day 1 and Day 8 of each 3-week cycle, up to 6 cycles.

  • CarboplatinDrug

    Carboplatin at AUC 5 IV on Day 1 of each 3-week cycle, up to 6 cycles.

  • GemcitabineDrug

    Gemcitabine 1250mg/m2 IV on Day 1 and Day 8 of each 3-week cycle, up to 6 cycles

Study groups in NCT05286619
Study groupRoleWhat they receive
Pembrolizumab plus Platinum and GemcitabineExperimentalPembrolizumab 200 mg will be administered as 30-minute IV infusion Day 1 of every 3 weeks. Pembrolizumab will be administered first followed by the platinum and gemcitabine infusions. Cisplatin will be administered on Day 1 and 8 of each 3-weeks treatment cycle with a dose of 35 mg/m2 for 60 minutes. Carboplatin will be administered on Day 1 of each 3-weeks treatment cycle given as a dose of AUC 5 for 60 minutes. Gemcitabine will be administered on Day 1 and 8 of each 3-weeks treatment given as a dose of 1250 mg/m2 for 30 minutes. AEs associated with pembrolizumab exposure, including coadministration with additional compounds, may represent an immunologic aetiology. If one or all of the chemotherapy components is discontinued, subjects can continue with pembrolizumab up to the full 35 cycles.
Receives: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Gemcitabine

What is being measured

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

  1. Objective Response Rate (ORR)

    To determine Objective Response Rate (ORR) per RECIST 1.1 to treatment of pembrolizumab plus platinum and gemcitabine in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.

    Measured: 24 months

Secondary outcomes (5)

  1. Overall Survival (OS)

    1. To evaluate the Overall Survival (OS) to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients

    Measured: 24 months

  2. Incidence of Treatment-Related Adverse Events (Safety and tolerability)

    To evaluate the number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.

    Measured: 24 months

  3. Progression Free Survival (PFS)

    1. To estimate Progression Free Survival (PFS) per RECIST 1.1 to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients

    Measured: 24 months

  4. Response duration (DOR)

    1. To estimate response duration (DOR) per RECIST 1.1 to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients

    Measured: 24 months

  5. ORR and OS correlation

    To evaluate the ORR and OS in correlation with PD-L1 Combined Positive Score (CPS)

    Measured: 24 months

Timeline

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

  1. First posted18 Mar 2022
  2. Study start22 Sep 2022
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2028 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05286619
Sponsor's protocol ID
IIT-CRMY(HN)2021001
Acronym
PIPER
Status last verified
Oct 2024
First submitted
11 Feb 2022
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Manuscript specific data will be shared with qualified external researches, access to patient-level data. These requests can be made via email to principal investigator of the study. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable law and regulations.

Publications

  • Cheong SC, Selvam B, Ho GF, Muhamad Nor I, Tan CK, Wong YF, Teo SH, Lim KP, Chai AWY, Yahya A, Wan Ishak WZ. Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia. BMJ Open. 2024 Dec 3;14(12):e076898. doi: 10.1136/bmjopen-2023-076898.

    PubMed 39627139

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Cisplatin and Carboplatin in people with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, run by University of Malaya at 1 site in Malaysia.

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 20 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Malaysia. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wan Zamaniah Wan Ishak, MBBS, MD (0379492120 ext. 2120, wzamaniah@ummc.edu.my), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 24 months). 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 NCT05286619, 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 15 Oct 2024.

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