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Head and Neck Squamous Cell CarcinomaPhase 1/2NCT03650764

Ramucirumab + Pembrolizumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 1/2 study testing Ramucirumab and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

The investigators hypothesize that inhibition of angiogenesis and PD-1 will be more effective than inhibition of PD-1 alone. The first step in pursuing proof of this hypothesis is to establish the safety and feasibility of combining ramucirumab with pembrolizumab, therefore the first part of this protocol is a… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Ramucirumab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
29 May 2019to 11 May 2026
Phase
Phase 1/2
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

  • Incurable HNSCC, defined as RM disease not amenable to cure by surgery and/or radiation therapy or patient with HNSCC declines or is ineligible for curative therapy
  • In phase I, oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, paranasal sinus, or salivary gland
  • In phase II, oral cavity, oropharynx, larynx, or hypopharynx
  • Disease Evaluation:
  • In phase I, evaluable or measurable disease.
  • In phase II, measurable disease per RECIST 1.1
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  • Prior Treatment:
  • For phase I, any number of lines of prior therapy for RM-HNSCC.
  • For phase II, no prior systemic therapy for RM-HNSCC.
  • At least 18 years of age.
  • Performance status 0-2 (ECOG).
  • Adequate blood and organ function as defined:
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST(SGOT) ≤ 3 x institutional upper limit of normal (IULN) and ALT(SGPT) ≤ 3 x IULN. In the setting of liver metastases, AST < 5 x IULN and ALT < 5 x IULN.
  • Creatinine ≤ 2 x ULN OR creatinine clearance ≥ 40 mL/min/1.73 m2
  • Urine protein to creatinine ratio (UPC) ≤ 1; if UPC ≥ 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < 1 g to be eligible
  • INR ≤ 1.5 x ULN (≤ 3.0 x ULN if on anticoagulation) and PTT ≤ 1.5 x ULN (<3 x ULN if on anticoagulation) [Patients are allowed to be on anticoagulation]
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to first dose of ramucirumab, through the dosing period, and for at least 28 days after.
  • Signed IRB approved written informed consent document.

Who cannot join

  • Phase II: prior PD-1 inhibitor for treatment of incurable HNSCC. For phase I, prior PD-1 inhibitor therapy in the incurable setting is permitted.
  • Radiation, chemotherapy, targeted or investigational therapy within 14 days of treatment start.
  • Major surgery, presence of a non-healing, non-malignant ulcer within 14 days of treatment start; History of significant tumor site bleeding within 14 days of study consent.
  • History of other malignancy ≤ 1 year previous with the exception of completely resected skin carcinoma or other cancers with a low risk of recurrence.
  • Cirrhosis at a level of Child-Pugh B (or worse), Cirrhosis of any degree with a history of hepatic encephalopathy or clinically meaningful ascites (from cirrhosis requiring diuretics or paracentesis).
  • Receiving any other investigational agents.
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  • Ongoing toxicity attributed to prior anti-cancer therapy that is > grade 1, except alopecia, anemia, fatigue or rash.
  • Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed, patients with CNS disease are eligible if they meet all other criteria for enrollment.
  • History of severe allergic reactions attributed to agents used in the study.
  • Serious uncontrolled inter-current illness within the 3 months prior to study entry or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving systemic steroid therapy (in dosing exceeding 20 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
  • Has an active autoimmune disease (i.e. rheumatoid arthritis, lupus, Sjogren's syndrome) that has required IV or subcutaneous systemic treatment in the past 6 months (excluding rituxin). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of system treatment.
  • GI perforation or fistula within 6 months of first dose of protocol therapy
  • History of GI issues such as inflammatory bowel disease, ulcerative colitis, or Crohn's disease.
  • Poorly controlled hypertension (defined as high blood pressure measurements [systolic blood pressures of ≥ 160 mmHg or diastolic blood pressures of > 100 mmHg] documented during the two-week interval prior to enrollment). Initiation or adjustment of antihypertensive medications to control blood pressure is permitted prior to study entry.
  • Arterial thromboembolic events (including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina) within 3 months prior to first dose of treatment.
  • GI Bleeding (grade 3 or 4) within 3 months prior to first dose.
  • Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 7 days of first dose of treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Prospective Phase I and II Trial of Ramucirumab + Pembrolizumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

The investigators hypothesize that inhibition of angiogenesis and PD-1 will be more effective than inhibition of PD-1 alone. The first step in pursuing proof of this hypothesis is to establish the safety and feasibility of combining ramucirumab with pembrolizumab, therefore the first part of this protocol is a de-escalation phase I trial of the combination of ramucirumab + pembrolizumab. Three participants will be treated at each dose level. De-escalation to the next dose level will occur if 2 or more participants experience dose-limiting toxicities (DLTs) attributable to ramucirumab during cycle 1. The key objective of the phase I trial is to establish the safety and the recommended phase 2 dose (RP2D) of ramucirumab for this novel combination regimen in patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC). The second step in pursuing proof of this hypothesis is to establish the efficacy of ramucirumab (using the RP2D) with pembrolizumab. The second part of this protocol is a single arm phase II trial combining ramucirumab + pembrolizumab. The primary objective of the phase II trial is to determine the tumor response rates (complete response (CR) and partial response (PR)) of the treatment combination given as first line therapy in patients with RM-HNSCC.

Being tested
Ramucirumab, Pembrolizumab
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.

  • RamucirumabDrug

    Also called Cyramza

    Ramucirumab is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab is commercially available

Study groups in NCT03650764
Study groupRoleWhat they receive
Phase I Dose Level 1 : Ramucirumab (10 mg/kg) + PembrolizumabExperimentalParticipants enrolled in Phase I Dose Level 1 received 10 mg/kg ramucirumab administered intravenously (IV) on Day 1. Pembrolizumab was administered as per standard of care (SOC) IV at a dose of 200 mg on Day 1. Each cycle was 21 days.
Receives: Drug: Ramucirumab; Drug: Pembrolizumab
Phase II: Ramucirumab (10 mg/kg) + PembrolizumabExperimentalParticipants enrolled in the Phase II portion received 10 mg/kg intravenous ramucirumab which was the recommended phase 2 dose (RP2D) determined during the Phase I portion on Day 1. Pembrolizumab was administered as per standard of care (SOC) IV at a dose of 200 mg on Day 1. Each cycle was 21 days.
Receives: Drug: Ramucirumab; Drug: Pembrolizumab

What is being measured

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

  1. Recommended Phase 2 Dose (RP2D) of Ramucirumab Combined With Fixed Dose Pembrolizumab (Phase I Participants Only)

    -The RP2D of ramucirumab is defined as the highest dose level at which fewer than 2 participants of a cohort of three participants experience a dose-limiting toxicity (DLT) during the first cycle.

    Measured: Completion of first cycle of treatment (each cycle is 21 days) for all participants enrolled in Phase I portion of study (estimated to be 2.5 months)

  2. Objective Response Rate of Ramucirumab and Pembrolizumab (Phase II Participants Only)

    • Objective response rate = number of participants with complete response + partial response as measured per RECIST 1.1
    • Complete response (CR)=Disappearance of all target lesions and non-target lesions along with normalizations of tumor marker level. 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 the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Through completion of treatment (median length of follow-up 162 days, full range 1-2240 days)

Secondary outcomes (10)
  1. Adverse Event Profile of the Combination of Ramucirumab and Pembrolizumab (Phase I and II Participants) as Measured by the Frequency of Adverse Events

    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

    Measured: Through 28 days after completion of treatment (median length of follow-up 183 days, full range 14-2240 days)

  2. Duration of Response (Phase II Participants Only)

    -Duration of response: The duration of response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Through completion of follow-up (median length of follow-up of 445 days, full range 14-2240 days)

  3. Kaplan-Meier Estimate of Median Progression-free Survival (PFS) (Phase II Participants Only)

    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive disease: At least a 20% increase in the sum of the 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 progressions).

    Measured: Through completion of follow-up (median length of follow-up of 445 days, full range 14-2240 days)

  4. Kaplan-Meier Estimate of Median Overall Survival (OS) (Phase II Participants Only)

    OS is defined as the duration of time from start of treatment to time of death (or last follow-up alive).

    Measured: Through completion of follow-up (median length of follow-up of 445 days, full range 14-2240 days)

  5. Changes in Quality of Life as Measured by Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) (Phase II Participants Only)

    • Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-H\&N Total Score (range 0-148) measures the sum of the physical, social, emotional, functional, and HNCS domains
    • The maximum score of 148 reflects the best quality of life.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

  6. Changes in Quality of Life as Measured by Functional Assessment of Cancer Therapy-Head and Neck Trial Outcome Index (FACT-H&N TOI) (Phase II Participants Only)

    • Includes 39 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, and 12 in head \& neck
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-H\&N TOI (range 0-96) measures the total score for the physical, functional, and HNCS domains but excludes the emotional and social domains
    • The maximum score of 96 reflects the best quality of life.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

  7. Changes in Quality of Life as Measured by Functional Assessment of Cancer Therapy-General (FACT-G) (Phase II Participants Only)

    • Includes 27 questions: 7 in physical well-being, 6 in emotional well-being, 7 in functional well-being, 7 in social well-being.
    • Scored from 0 (not at all) to 4 (very much)
    • Higher scores indicated worse physical and emotional well-being and better social/family and functional well-being
    • The FACT-G Total Score (range 0-108) measures the sum of the physical, social, emotional, and functional domains but excludes the HNCS domain
    • The maximum score of 108 reflects the best quality of life.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

  8. Changes in Quality of Life as Measured by The European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-30) - Global Health Status (Phase II Participants Only)

    EORTC QLQ-C30: this has a total score, one general quality of life (QoL), and one "within the last week" subscale, as well as a general health item and a single overall QoL item. This study does not use current empirical guidelines for the EORTC-QLQ-30 global score with the understanding that both the magnitude and variance of scores vary considerably from patient to patient, from one time point to another and by such factors as disease condition, age, and comorbidity. The participants can choose from 1-4 with 1 being Not At All and 4 being Very Much. A high scale score represents a higher response level but these differ based on the type of sub-scale. Per the QLQ-C30 scoring manual, a high score for the global health status / QoL represents a high QoL, The total score range was 0-100.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

  9. Changes in Quality of Life as Measured by The European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-30) - Functional Scale (Phase II Participants Only)

    EORTC QLQ-C30: this has a total score, one general quality of life (QoL), and one "within the last week" subscale, as well as a general health item and a single overall QoL item. This study does not use current empirical guidelines for the EORTC-QLQ-30 global score with the understanding that both the magnitude and variance of scores vary considerably from patient to patient, from one time point to another and by such factors as disease condition, age, and comorbidity. The participants can choose from 1-4 with 1 being Not At All and 4 being Very Much. A high scale score represents a higher response level but these differ based on the type of sub-scale. Per the QLQ-C30 scoring manual, high score for a functional scale represents a high / healthy level of functioning. The total score range was 0-100.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

  10. Changes in Quality of Life as Measured by The European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-30) - Symptom Scale (Phase II Participants Only)

    EORTC QLQ-C30: this has a total score, one general quality of life (QoL), and one "within the last week" subscale, as well as a general health item and a single overall QoL item. This study does not use current empirical guidelines for the EORTC-QLQ-30 global score with the understanding that both the magnitude and variance of scores vary considerably from patient to patient, from one time point to another and by such factors as disease condition, age, and comorbidity. The participants can choose from 1-4 with 1 being Not At All and 4 being Very Much. A high scale score represents a higher response level but these differ based on the type of sub-scale. Per the QLQ-C30 scoring manual, a high score for a symptom scale / item represents a high level of symptomatology / problems. The total score range was 0-100.

    Measured: Baseline, start of cycle 2 (each cycle is 21 days), and start of cycle 5 (estimated to be 12 weeks)

Timeline

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

  1. First posted29 Aug 2018
  2. Study start29 May 2019
  3. Primary completion11 May 2026
  4. Study completion11 May 2026

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03650764
Sponsor's protocol ID
201809094
Status last verified
Aug 2026
First submitted
27 Aug 2018
Last updated
17 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Adkins D, Ley JC, Liu J, Oppelt P. Ramucirumab in combination with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma: a single-centre, phase 1/2 trial. Lancet Oncol. 2024 Jul;25(7):888-900. doi: 10.1016/S1470-2045(24)00204-3. Epub 2024 Jun 5.

    PubMed 38851207

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ramucirumab and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.

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 22 inclusion and 18 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 17 Aug 2026. 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 United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 17 Aug 2026). 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?

Recommended Phase 2 Dose (RP2D) of Ramucirumab Combined With Fixed Dose Pembrolizumab (Phase I Participants Only) (time frame: Completion of first cycle of treatment (each cycle is 21 days) for all participants enrolled in Phase I portion of study (estimated to be 2.5 months)). 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 NCT03650764, 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 17 Aug 2026.

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