Pembrolizumab Plus Lenvatinib in Unresectable Cutaneous Angiosarcoma Patients

NCT06673628 | Recruiting Phase 2 DMC

• 1 other identifier: NCCH2213
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 5

Brief Summary

Cutaneous angiosarcoma is a rare cancer for which effective treatment has not been developed sufficiently. Still, because it often occurs in elderly people, the number of patients is increasing due to the aging population. Cutaneous angiosarcoma is difficult to completely remove by surgery, and recurrence and metastasis after surgery are not uncommon. Therefore, chemotherapy, radiation therapy, and a combination of these are currently widely used as treatments. Traditionally, the anticancer drug used for cutaneous angiosarcoma was mainly doxorubicin. In recent years, it has been reported that cancer shrank in 18% of patients after two months of paclitaxel administration in a clinical trial. Therefore, paclitaxel has become more commonly used for cutaneous angiosarcoma. Other options include anthracycline anticancer drugs and gemcitabine. However, even with these anticancer drugs (and radiation therapy), cutaneous angiosarcoma progresses quickly, and some reports have said that the 5-year survival rate is 9%. This study is planned to develop a safer and more effective treatment for cutaneous angiosarcoma and will include 38 participants. In this study, eligible participants will receive combination chemotherapy with 200 mg of pembrolizumab (injection liquid, once every 3 weeks) and 20 mg of lenvatinib (capsule, once daily) for up to approximately two years as protocol treatment unless the criteria for termination meet. Before, during, and after the protocol treatment, participants will undergo many examinations and evaluations, including blood tests, urine tests, and imaging tests (e.g., x-ray, CT scan, or MRI) to assess the safety and efficacy of the protocol treatment.

Conditions

Angiosarcoma of Skin; Angiosarcoma Metastatic

Keywords

pembrolizumab; lenvatinib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) by central review

  ORR by central review is the combined incidence of complete response (CR) and partial response (PR) of Best Overall Response in the full analysis set (FAS), and is assessed by the pre-appointed independent data monitoring committee. Best Overall Response is determined as the best overall response evaluated among CR, PR, SD (stable disease), PD (progressive disease), and NE (not evaluable).

  Overall Response is assessed every 6 weeks until 24 weeks after initiation of protocol treatment and every 12 weeks after 25 weeks until PD confirmation or post-study treatment initiation, an estimated average of 1 year.

Secondary Outcomes (9)

• Overall Response Rate (ORR) by institutional review

  Overall Response is assessed every 6 weeks until 24 weeks after initiation of protocol treatment and every 12 weeks after 25 weeks until PD confirmation or post-study treatment initiation, an estimated average of 1 year.

• Progression-free survival (PFS)

  PFS is assessed every 6 weeks until 24 weeks after initiation of protocol treatment and every 12 weeks after 25 weeks until PD confirmation or post-study treatment initiation, an estimated average of 1 year.

• Overall Survival (OS)

  OS is observed on days 1 and 8 on Course 1, days 1 on and after Course 2, at completion/termination, and every 6 months after completion/termination until the participant's death or loss to follow-up, an estimated average of 2 years.

• Disease Control Rate

  Disease Control Rate is assessed every 6 weeks until 24 weeks after initiation of protocol treatment, and every 12 weeks after 25 weeks until PD confirmation or post-study treatment initiation, an estimated average of 1 year.

• Incidence of Adverse Events (AEs)

  An AE is observed and evaluated on days 1 and 8 on Course 1, days 1 on and after Course 2, at completion/termination of the study protocol, and until 30 days after the last dose of the study drug.

Study Arms (1)

Pembrolizumab plus lenvatinib

EXPERIMENTAL

Drug: Pembrolizumab plus Lenvatinib

Interventions

Pembrolizumab plus Lenvatinib DRUG

One course is fixed at 21 days, and the length of course is not extended or shortened. Participants receive 200 mg of pembrolizumab injection intravenously over approximately 30 minutes on day 1 of each course, and take 20 mg of lenvatinib capsules orally once daily, preferably at the same time each day. Treatment with pembrolizumab and lenvatinib will be continued for up to 35 courses unless the criteria for termination of protocol treatment are met.

Pembrolizumab plus lenvatinib

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically diagnosed with cutaneous angiosarcoma.
• Unresectable primary or metastatic disease.
• No spinal metastases that require radiotherapy or surgical intervention.
• No pericardial effusion, pleural effusion, or ascites that require treatment.
• Age at enrollment: 18 years or older and 85 years or younger.
• The most recent performance status score (ECOG) within 14 days prior to enrollment is 0 or 1.
• A contrast-enhanced CT/MRI (head, neck, chest, abdomen, pelvis: slice thickness 5 mm or less) performed within 14 days prior to enrollment or have at least one measurable lesion that can be confirmed to be present on the surface of the body by visual inspection (for patients with contrast allergy or renal function deterioration, plain CT is allowed).
• Cohort A (untreated patients): Cutaneous angiosarcoma without prior therapy. Cohort B (previously treated patients): Cutaneous angiosarcoma with prior therapy.
• Have adequately controlled BP with or without antihypertensive medications (of 2 or less counted by components), defined as BP \<=150/90 mmHg with no change in antihypertensive medications within 7 days prior to enrollment.
• Wounds (e.g., those after a surgical procedure or trauma) have healed at enrollment.
• Did not have major surgery within 21 days prior to the first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• Laboratory tests performed within 14 days before the enrollment date meet the following criteria: (1) to (10). However, patients should not receive granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 14 days before the day of blood collection.
• (1) Neutrophil count \>=1,500/mm3 (2) Platelet count \>=10×104/mm3 (3) Hemoglobin \>=9.0 g/dL (4) AST \<=100 U/L (5) ALT\<=100 U/L (6) Total bilirubin \<=1.5 mg/dL (7) Serum creatinine \<=1.5 mg/dL (8) Creatinine/clearance \>=30 mL/min (Cockcroft-Gault). (Even if the calculated value is less than 30 mL/min, it can be registered if the value is more than 30 mL/min by the 24-hour urine collection method).
• (9) Urine protein \<1 g/24 hours. Note: Participants with proteinuria \>=2+ on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• (10) PT-INR \<=1.5 13) Male patients agree to use highly effective contraception and not donate sperm during treatment and for at least 120 days after the last dose of the investigational drugs.

You may not qualify if:

• Persons previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2 agents, or agents targeting other co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
• Individuals previously treated with lenvatinib or another angiogenesis inhibitor, including treatment for other cancer types.
• Patients who are likely to be cured with chemoradiotherapy, at the discretion of the treating physician.
• Patients who received radiation therapy within 14 days prior to enrollment or patients with radiation therapy-related toxicities at enrollment.
• Patients positive for either HIV antibody, HBs antigen, or HCV antibody.
• Patients of HBs antigen-negative, HBs antibody, or HBc antibody-positive, and HBV-DNA assay-positive.
• Patients receiving live or live attenuated vaccines within 30 days of enrollment.
• Patients who received other investigational products or used investigational medical devices within 28 days prior to enrollment.
• Patients diagnosed as being in an immunocompromised state or patients treated with long-term systemic steroidal therapy or other immunosuppressive therapies in the 14 days prior to enrollment.
• Patients with other malignancies requiring progressive or aggressive treatment within the past 3 years.
• Patients with active CNS metastases or carcinomatous meningitis.
• Patients with severe (\>= Grade 3) hypersensitivity to pembrolizumab or lenvatinib additives.
• Patients with active autoimmune disease requiring systemic treatment, excluding replacement therapy within the past 2 years.
• Patients with a history of interstitial lung disease/pneumonitis complicated by interstitial lung disease/pneumonitis or interstitial lung disease/pneumonitis requiring steroid administration (non-infectious).
• Patients with active infections requiring systemic treatment at enrollment.

Sponsors & Collaborators

• National Cancer Center, Japan: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

National Cancer Center Hospital East

Kashiwa, Japan

RECRUITING

University Hospital Kyoto Prefectural University of Medicine

Kyoto, Japan

RECRUITING

Nagoya City University Hospital

Nagoya, Japan

RECRUITING

Keio University Hospital

Tokyo, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, Japan

RECRUITING

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Central Study Contacts

Dai Ogata, M.D., Ph.D.

CONTACT

+81.3.3542.2511; dogata@ncc.go.jp

Eiji Nakano, M.D., Ph.D.

CONTACT

+81.3.3542.2511; einakano@ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 5, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5)