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Recurrent Head and Neck CancerPhase 2Rambro2NCT05980000

Ramucirumab and Pembrolizumab vs Pembrolizumab Monotherapy in PD-L1 Positive Head and Neck Squamous-Cell Carcinoma

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

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This is a phase 2 study investigating the efficacy of ramucirumab in combination with pembrolizumab compared to pembrolizumab monotherapy. Ramucirumab is a VEGFR-2 inhibitor believed to potentially enhance the efficacy of PD-1 inhibitors such as pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older
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
37 participants
Where
1 siteUnited States
Study dates
27 Oct 2023to 30 Jun 2030
Phase
Phase 2

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 RM-HNSCC, defined as RM disease or second or subsequent primary HNSCC not amenable to cure by surgery and/or radiation therapy or patient declines or is ineligible for curative therapy. Eligible primary tumor sub-sites include oral cavity, oropharynx, larynx and hypopharynx only.
  • PD-L1 positive (CPS ≥1) disease, based on local IHC assay using 22C3 antibody.
  • Measurable disease per RECIST 1.1.
  • No prior systemic therapy for RM-HNSCC. RM disease developing within 6 months of completion of either a) systemic platinum or cetuximab therapy given as a component of a curative-intent multi-modality regimen or b) radiation therapy and/or surgery is eligible.
  • At least 18 years of age.
  • ECOG performance status 0-1.
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  • Normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN. In the setting of liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5.0 x IULN
  • Creatinine ≤ 1.5 x ULN. If patient has creatinine > 1.5 x ULN, then 24 hour urine collection must be performed and creatinine clearance must be ≥ 40 mL/min by Cockcroft-Gault
  • Urine protein to creatinine ratio (UPC) ≤ 1; if UPC > 1, then a 24-hour urine protein must be assessed and patient must have a 24-hour urine protein value < 1 g to be eligible
  • INR ≤ 1.5 (≤ 3.0 if on warfarin) and PTT ≤ 1.5 x ULN (Patients are allowed to be on anticoagulation)
  • The effects of Ramucirumab on the developing human fetus are unknown. For this reason and because VEGFR2 inhibiting agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 28 days after completion of the study.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • PD-L1 negative (CPS 0) disease, based on local IHC assay using 22C3 antibody.
  • Cutaneous or nasopharynx SCC.
  • Major surgery within 28 days prior to C1D1, minor surgery or subcutaneous venous access device placement within 7 days prior to C1D1, history of significant tumor site bleeding within 14 days prior to C1D1, or elective or planned major surgery to be performed during the course of the clinical trial.
  • Palliative radiation therapy within 2 weeks of C1D1.
  • Serious or non-healing, non-malignant wound, ulcer, or bone fracture within 28 days prior to C1D1.
  • A history of other malignancy ≤ 1 year previous with the exception of completely resected skin carcinoma or other cancers with a low risk (<10%) of recurrence over the next 2 years.
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  • 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).
  • Currently receiving any other investigational agents.
  • Ongoing toxicity attributed to prior anti-cancer therapy that is > grade 1, except alopecia, anemia, lymphopenia, xerostomia, fatigue or rash.
  • Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed and patient has completed a 2 week washout, patients with CNS disease are eligible if they meet all other criteria for enrollment.
  • A history of severe allergic reactions attributed to compounds of similar chemical or biologic composition to Ramucirumab or other agents used in the study.
  • Serious uncontrolled intercurrent illness within the 3 months prior to study entry including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of intense immunosuppressive therapy within 7 days prior to C1D1.
  • Active autoimmune disease (i.e. rheumatoid arthritis, lupus) that has required IV or subcutaneous systemic treatment in the past 6 months prior to C1D1 (excluding Rituxan). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • GI perforation or fistula within 6 months of C1D1. Malignant oral fistulas are not excluded.
  • History of inflammatory bowel disease, ulcerative colitis, or Crohn's disease.
  • Poorly controlled hypertension (defined as serial high blood pressure measurements [systolic blood pressures of > 160 mmHg or diastolic blood pressures of > 100 mmHg] documented during the four-week interval prior to C1D1) despite standard medical management. 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 6 months, prior to C1D1.
  • Deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") within 3 months prior to C1D1.
  • Any bleeding (grade 3 or 4) within 3 months prior to C1D1.
  • Receiving chronic antiplatelet therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
  • Current, active bleeding (within 14 days prior to C1D1) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices), if patients are taking an oral anticoagulant or low molecular weight heparin. Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or LMWH prior to C1D1.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to C1D1.

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: Open-Label, Randomized Phase 2 Trial of Ramucirumab in Combination With Pembrolizumab Versus Pembrolizumab Alone as First-Line Treatment of PD-L1 Positive, Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma (RM-HNSCC)

This is a phase 2 study investigating the efficacy of ramucirumab in combination with pembrolizumab compared to pembrolizumab monotherapy. Ramucirumab is a VEGFR-2 inhibitor believed to potentially enhance the efficacy of PD-1 inhibitors such as pembrolizumab.

Being tested
Ramucirumab, Pembrolizumab
Keywords
PD-L1 positive RM-HNSCC, RM-HNSCC, oral cavity HNSCC, oropharynx HNSCC, larynx HNSCC, hypopharynx HNSCC
Medical subject headings
Head and Neck Neoplasms, 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 administered at a dose of 10 mg/kg over 60 minutes.

  • PembrolizumabDrug

    Also called MK-3475, Keytruda

    Pembrolizumab is administered at a flat dose of 200 mg over 30 minutes.

Study groups in NCT05980000
Study groupRoleWhat they receive
Arm 1: Ramucirumab and PembrolizumabExperimentalPatients receive ramucirumab IV and pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.
Receives: Drug: Ramucirumab; Drug: Pembrolizumab
Arm 2: Pembrolizumab monotherapyActive comparatorPatients receive pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR is defined as the number of patients with a complete response (CR) and a partial response (PR) by RECIST 1.1 criteria. A CR is defined as the disappearance of all target lesions, reduction in pathological lymph nodes to <10 mm in short axis, and disappearance of all non-target lesions with normalization of tumor marker level. A PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: From start of study treatment through completion of treatment (estimated to be 24 months)

Secondary outcomes (4)

  1. Duration of Response (DoR)

    Duration of overall response is measured from the time criteria are met for a CR or PR per RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Duration of overall CR is measured from the time criteria are met for a CR per RECIST 1.1 until the first date that progressive disease is objectively documented.

    Measured: From time criteria is met for CR or PR through completion of treatment (estimated to be 1 year and 40 weeks)

  2. Progression-Free Survival (PFS)

    PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first.

    Measured: From start of study treatment through 5 years

  3. Overall Survival (OS)

    OS is defined as the time from start of treatment to the date of death, censored at the last follow-up otherwise.

    Measured: From start of study treatment through 5 years

  4. Incidence rate, frequency, and severity of adverse events (AEs)

    AEs will be assessed using CTCAE v4.0 and summarized by arm.

    Measured: From start of study treatment through 30 days after last dose (expected to be 2 years and 1 month)

Timeline

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

  1. First posted7 Aug 2023
  2. Study start27 Oct 2023
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2030 (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
Randomised
Intervention model
Parallel groups
Model description
Patients will be randomized on a 2:1 basis to Arm 1 or Arm 2.
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05980000
Sponsor's protocol ID
202308161
Acronym
Rambro2
Status last verified
Mar 2026
First submitted
30 Jul 2023
Last updated
31 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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