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

NCT05286619 | Recruiting Phase 2

• 1 other identifier: IIT-CRMY(HN)2021001
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (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.

  24 months

Secondary Outcomes (5)

• Overall Survival (OS)

  24 months

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

  24 months

• Progression Free Survival (PFS)

  24 months

• Response duration (DOR)

  24 months

• ORR and OS correlation

  24 months

Other Outcomes (3)

• Genetic variation

  24 months

• Microbiome profiling

  24 months

• Circulatory immune cells correlations

  24 months

Study Arms (1)

Pembrolizumab plus Platinum and Gemcitabine

EXPERIMENTAL

Pembrolizumab 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.

Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Gemcitabine

Interventions

Pembrolizumab DRUG

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

Pembrolizumab plus Platinum and Gemcitabine

Cisplatin DRUG

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.

Pembrolizumab plus Platinum and Gemcitabine

Carboplatin DRUG

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

Pembrolizumab plus Platinum and Gemcitabine

Gemcitabine DRUG

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

Pembrolizumab plus Platinum and Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Malaya: lead
• Cancer Research Malaysia: collaborator
• Kuala Lumpur General Hospital: collaborator
• National Cancer Institute, Malaysia: collaborator
• Merck Sharp & Dohme LLC: collaborator
• My Starfish Foundation: collaborator
• Yayasan Sime Darby: collaborator
• Yayasan PETRONAS: collaborator

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

RECRUITING

Related Publications (1)

• 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.

  PMID: 39627139 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Cisplatin; Carboplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Wan Zamaniah Wan Ishak, MBBS, MD

  University of Malaya

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wan Zamaniah Wan Ishak, MBBS, MD

CONTACT

0379492120; wzamaniah@ummc.edu.my

Suganiya Rama Rao

CONTACT

0379492120; suganiya@ummc.edu.my

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Dr

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: March 18, 2022
• Study Start: September 22, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: From 22 Sept 2022 till June 2026
• Access Criteria: 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.

Locations

MY (1)