Pilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma

NCT02303041 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-29839NCI-2014-02200SKIN0020NCT02303041
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot trial studies how well sonidegib and buparlisib work in treating patients with basal cell carcinoma that has spread to other places in the body. Sonidegib and buparlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Carcinoma, Basal Cell; Recurrent Skin Cancer; Skin Neoplasms; Basal Cell Nevus Syndrome

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Response was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, and reported as overall response rate (ORR), comprised of the sum of complete response (CR) rate and partial response (PR) rate. * 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

  Up to 2 years

Secondary Outcomes (4)

• Median Duration of Response

  up to 12 weeks

• Adverse Event Frequency

  Up to 30 days post-treatment

• Changes in Gene Expression Profiles of BCCs Including Hedgehog Pathway and PI3K Pathways

  Baseline to 2 years

• Gene Expression Profiles (Correlation of Particular Gene Expression Profiles and Response to LB Therapy Will be Assessed.)

  up to 2 years post-treatment

Study Arms (2)

BCC Smoothened inhibitor-naive

EXPERIMENTAL

Participants with locally advanced or metastatic basal cell carcinoma (BCC) and naive to treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.

Drug: Buparlisib; Drug: Sonidegib

BCC refractory or relapsed after Smoothened inhibitor

EXPERIMENTAL

Participants with locally advanced or metastatic basal cell carcinoma (BCC) that is refractory or relapsed after treatment with Smoothened inhibitors receive sonidegib and buparlisib in repeating 28-day cycles in the absence of disease progression or unacceptable toxicity.

Drug: Buparlisib; Drug: Sonidegib

Interventions

Buparlisib DRUG

Administered orally at starting dose of 80 mg/day

Also known as: BKM120, PI3K inhibitor BKM120

BCC Smoothened inhibitor-naive; BCC refractory or relapsed after Smoothened inhibitor

Sonidegib DRUG

Administered orally at starting dose of 200 mg/day

Also known as: Sonidegib phosphate, Odomzo, Erismodegib, LDE225

BCC Smoothened inhibitor-naive; BCC refractory or relapsed after Smoothened inhibitor

Eligibility Criteria

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

You may qualify if:

• Able to understand and sign informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Metastatic BCC, histologic confirmation of distant BCC metastasis
• Metastatic disease, target lesion must be measurable using computed tomography (CT) or magnetic resonance imaging (MRI)
• Locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery
• Nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above
• COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapy
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 80 x10\^9/L
• Hemoglobin (Hb) \> 9 g/dL or values ≥ lower limit of normal (LLN) for site-specific lab
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range \[or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present\]
• Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well-documented Gilbert Syndrome)

You may not qualify if:

• Prior treatment with a P13K inhibitor
• Known hypersensitivity to buparlisib or to its excipients
• Untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy
• Acute or chronic liver, renal disease or pancreatitis
• Baseline creatinine kinase (CK) \> ULN
• The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire:
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of ≥ 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Diarrhea ≥ CTCAE grade 2
• Active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc \> 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions

Sponsors & Collaborators

• Anne Chang: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Tran DC, Moffat A, Brotherton R, Pague A, Zhu GA, Chang ALS. An exploratory open-label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas. J Am Acad Dermatol. 2018 May;78(5):1011-1013.e3. doi: 10.1016/j.jaad.2017.11.031. Epub 2017 Nov 23. No abstract available.

  PMID: 29175429 RESULT

MeSH Terms

Conditions

Carcinoma, Basal Cell; Skin Neoplasms; Basal Cell Nevus Syndrome

Interventions

NVP-BKM120; sonidegib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

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

alschang@stanford.edu

650-723-6316

Study Officials

• Anne Lynn Chang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Dermatology

Model Details: Cohort assignment based on disease status.

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: November 27, 2014
• Study Start: February 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: January 29, 2019
• Results First Posted: January 29, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)