Pulsed Dose Chemotherapy Plus Pembrolizumab in Recurrent/Metastatic HNSCC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDan Zandberg
About this trial
The rationale for the new sequence of pulsed dose chemotherapy proposed in this trial is based on the hypotheses that current standard dosing of chemotherapy plus pembrolizumab ultimately suppresses the immune system and has a negative effect on the efficacy of the anti-PD-1 monoclonal antibody (mAb) therapy and that chemotherapy given after anti-PD-1 mAb therapy is associated with higher efficacy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
PD-L1 Combined Positive Score (CPS) >1
Age > 18 years.
Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-2
Disqualifiers
Patients should not have had prior systemic therapy alone administered in the recurrent/ or metastatic setting. If a patient received platinum based systemic therapy which was completed more than 6 months prior to signing consent given as part of multimodal curative intent treatment for locally advanced HNSCC (This includes both definitive concurrent chemoradiation and adjuvant chemoradiation) the patient is still eligible,
A patient cannot have received prior anti-PD-1 or anti-PD-L1 monoclonal antibody (mAb) therapy as systemic therapy for the treatment of recurrent/metastatic disease. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of multimodality curative intent treatment of locally advanced disease are still eligible as long as it has been at least 1 year since prior therapy. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of radiation for locoregional recurrence will be eligible as long as it has been 1 year since prior therapy.
Squamous cell carcinoma of the skin or of salivary gland origin.
Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism or Sjogren's syndrome will not be excluded from the study.
Trial design
Design model
Single group
Treatments tested in this trial
Pembrolizumab
DrugImmunotherapy that works by helping the immune system to kill cancer cells by targeting and blocking a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
Carboplatin
DrugA chemotherapy drug that contains the metal platinum. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their DNA.
Paclitaxel
DrugA chemotherapeutic agent used as a treatment for various cancers; paclitaxel is a mitotic inhibitor.
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: Pembrolizumab + Carboplatin with PaclitaxelExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
6-month Progression-free Survival (PFS)
Proportion of patients alive and without disease progression at 6 months after starting treatment, per RECIST v1.1. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame
At 6 monthsSecondary outcomes
1
Adverse Events (AE) and Serious Adverse Events (SAE) Related to Treatment
Proportion of patients that experience Adverse Events or Serious Adverse Events related to treatment, per CTCAE v5.0. The maximum grade for each toxicity type will be recorded for each patient.
Time frame
Up to 2 years2
Overall Response Rate (ORR)
Proportion of patients with Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Up to 2 years3
Duration of Response (DOR)
Time from start of treatment to disease progression or death in patients who achieve Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Up to 4 years4
Overall Survival (OS)
Median number of months from start of treatment that patients remain alive.
Time frame
Up to 4 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Dan Zandberg
Lead sponsor
University of Pittsburgh
Sponsor institution
Source ClinicalTrials.gov