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

NCT ID: NCT03650764

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-29
• Study Completion Date: 2025-12-31

Brief 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 de-escalation phase I trial of the combination of ramucirumab + pembrolizumab. 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.

Conditions

Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I: Ramucirumab + Pembrolizumab

-Ramucirumab will be administered IV over 1 hour on Day 1 of each 21-day cycle. Pembrolizumab will be administered as per standard of care (IV at a dose of 200 mg over 30 minutes on Day 1 of each 21-day cycle). On Day 1, pembrolizumab will be given after ramucirumab.

Group Type: EXPERIMENTAL

Ramucirumab

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is commercially available

Peripheral blood

Intervention Type: PROCEDURE

-Baseline

Phase II: Ramucirumab + Pembrolizumab

-Patients will be treated with ramucirumab at the RP2D on Day 1 and SOC pembrolizumab (200 mg IV over 30 minutes) on Day 1 of each 21-day cycle.

Group Type: EXPERIMENTAL

Ramucirumab

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is commercially available

EORTC QLQ-30

Intervention Type: OTHER

-Screening, start of cycle 2, start of cycle 5

FACT H&N

Intervention Type: OTHER

-Screening, start of cycle 2, start of cycle 5

Peripheral blood

Intervention Type: PROCEDURE

-Baseline

Interventions

Ramucirumab

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

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is commercially available

Intervention Type: DRUG

EORTC QLQ-30

-Screening, start of cycle 2, start of cycle 5

Intervention Type: OTHER

FACT H&N

-Screening, start of cycle 2, start of cycle 5

Intervention Type: OTHER

Peripheral blood

-Baseline

Intervention Type: PROCEDURE

Other Intervention Names

Cyramza; Keytruda

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas R Adkins, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38851207 (View on PubMed)

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201809094

Identifier Type: -

Identifier Source: org_study_id