Ramucirumab + Pembrolizumab for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Overseen byDouglas R Adkins, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Washington University School of Medicine

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with incurable head and neck squamous cell carcinoma (HNSCC) that can't be treated by surgery or radiation, or if the patient declines such treatments. Participants need to have certain blood counts and organ functions within specific ranges, no severe allergies to study agents, no recent heart attacks or strokes, and must not be pregnant. They should agree to use contraception and have not received certain therapies recently.

Inclusion Criteria

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; INR ≤ 1.5 x ULN (≤ 3.0 x ULN if on anticoagulation) and PTT ≤ 1.5 x ULN (<3 x ULN if on anticoagulation); Women of childbearing potential and men must agree to use adequate contraception

Signed IRB approved written informed consent document

My cancer is in my mouth, throat, voice box, nose, or salivary glands.

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Exclusion Criteria

I have had PD-1 inhibitor therapy for incurable head and neck cancer.

I haven't had cancer treatment like radiation or chemotherapy in the last 14 days.

I haven't had major surgery or significant bleeding from the tumor site in the last 14 days.

See 14 more

Treatment Details

Interventions

Pembrolizumab (Monoclonal Antibodies)
Ramucirumab (Monoclonal Antibodies)

Trial OverviewThe trial tests combining Ramucirumab with Pembrolizumab versus Pembrolizumab alone in treating HNSCC. Phase I determines the safe dose of Ramucirumab when combined with Pembrolizumab while phase II evaluates how effective this combination is as a first-line treatment by looking at tumor response rates.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Phase II: Ramucirumab + PembrolizumabExperimental Treatment5 Interventions

-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 II: Phase I: Ramucirumab + PembrolizumabExperimental Treatment3 Interventions

-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.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸 Approved in United States as KEYTRUDA for: