Pembrolizumab With or Without Vismodegib in Treating Metastatic or Unresectable Basal Cell Skin Cancer

NCT02690948 | Completed Phase 1 Results DMC FDA Drug

• 5 other identifiers: IRB-34925NCI-2015-01869350P30CA124435SKIN0031
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1-2 trial studies how well pembrolizumab with or without vismodegib works in treating patients with skin basal cell cancer that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, are checkpoint inhibitors that stimulate immune response. Vismodegib may stop the growth of tumor cells by blocking signals needed for cell growth.

Conditions

Skin Basal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The overall response rate (ORR) of participants with unresectable or metastatic basal cell carcinoma (BCC) after treatment with A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, will be assessed as the percentage of participants with partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, after 9 and 18 weeks of treatment. ORR is calculated as the ratio of patients with CR or PR as a percentage of the participants evaluable for OR. RECIST criteria: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria

  18 weeks

Secondary Outcomes (5)

• Percentage of Participants Experiencing Adverse Events

  up to 2 years

• Related Adverse Events

  up to 2 years

• Duration of Response (DOR)

  up to 2 years

• Overall Survival (OS)

  1 year

• Progression-free Survival (PFS)

  1 year

Study Arms (2)

Pembrolizumab Monotherapy

EXPERIMENTAL

Participants who previously received vismodegib and subsequently progressed will receive pembrolizumab IV over 30 minutes on day 1. Cycles are every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab

Pembrolizumab plus Vismodegib Combination Therapy

EXPERIMENTAL

Participants who have not progressed while receiving vismodegib will receive pembrolizumab IV over 30 minutes on day 1 and take vismodegib 150 mg by mouth daily. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Vismodegib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Pembrolizumab Monotherapy; Pembrolizumab plus Vismodegib Combination Therapy

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Pembrolizumab plus Vismodegib Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Histologically-proven basal cell carcinoma (BCC) in which curative resection is unlikely without significant morbidity, or have nodal or distantly metastatic disease which has progressed on vismodegib (Arm 1) or has achieved partial response or stable disease on smoothened inhibitor (Arm 2). Individuals who are intolerant or have a medical contra-indication to smoothened inhibitor will be enrolled into Arm 1.
• Have measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
• ≥ 18 years of age on day of consent.
• Willing to provide tissue from a core or excisional biopsy of a tumor lesion up to 6 weeks (42 days) prior to initiation of treatment on Day 1, or availability of adequate archival specimens.
• Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 or 1
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL, or ≥ 5.6 mmol/L, without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 60 mL/min for subject(s) with creatinine levels \> 1.5 x ULN
• Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN, OR ≤ 5 x ULN for subjects with liver metastases
• alanine aminotransferase (ALT) ≤ 2.5 x ULN, OR ≤ 5 x ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy, in which case PT/INR must be within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy, in which case PTT must be within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Currently receiving investigational study therapy, or has received investigational study therapy, or used an investigational device, within 4 weeks of the first dose of treatment.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (EXCEPTIONS: topical, intraarticular, intralesional, and inhaled steroids)
• Known history of active Bacillus Tuberculosis (TB) infection
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has received an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1, or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has received chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1, or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (EXCEPTION: Subjects with ≤ Grade 2 neuropathy may qualify for the study).
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Known additional malignancy that is progressing or requires active treatment. (EXCEPTIONS: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer)
• Carcinomatous meningitis without consideration of clinical stability
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intraarticular, inhaled, and intralesional doses of steroids are allowed at screening and during the study.
• Known history of, or any evidence of active, non-infectious pneumonitis that required steroids or current pneumonitis.
• Active infection requiring systemic therapy.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Anne Chang: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell

Interventions

pembrolizumab; HhAntag691

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell

Results Point of Contact

• Title: Anne Lynn S. Chang, Associate Professor of Dermatology
• Organization: Stanford University

alschang@stanford.edu

650-721-7151

Study Officials

• Anne Lynn S Chang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Dermatology

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 24, 2016
• Study Start: February 1, 2016
• Primary Completion: November 30, 2017
• Study Completion: August 29, 2018
• Last Updated: March 8, 2019
• Results First Posted: March 8, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)