Abemaciclib for Kaposi Sarcoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must be taking: Antiretrovirals
Must not be taking: CYP3A4 inhibitors
Disqualifiers: Chemotherapy, Immunotherapy, Pregnancy, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
Kaposi Sarcoma (KS) is common in people with human immunodeficiency virus (HIV) but can also occur in people who do not have HIV. KS tumors usually involve the skin, but may also involve lymph nodes, lungs, bone, and gastrointestinal tract. Researchers want to see if a drug that is currently used to treat a type of breast cancer can help.
Objective:
To find a safe dose of abemaciclib to treat KS and to see if it can shrink lesions or tumors.
Eligibility:
People ages 18 and older with KS.
Design:
Participants will be screened with some or all of the following:
Medical history
Physical exam
Blood and urine tests
Chest x-ray and/or computed tomography scans
Lung or gastrointestinal tract exam with an endoscope (a flexible instrument to examine the interior of the organ)
Medicine review
Heart function tests
KS lesion assessment
Skin sample from a KS lesion
Treatment will be given in 28-day cycles. Participants will take the study drug tablets by mouth everyday. They will keep a medicine diary. They will get the study drug until their cancer gets worse or they have unacceptable side effects.
Participants will have a study visit at the beginning of each cycle. At these visits, they will repeat some screening tests. They may have medical photographs taken of body surfaces. They may complete questionnaires about their quality of life. They may give skin and saliva samples. For skin samples, an area of skin will be numbed. A small circle of skin over an area affected by KS will be removed.
Participants will have follow-up visits for up to 2 years after treatment ends.
Do I have to stop taking my current medications for the trial?
The trial does not specify if you must stop taking your current medications, but you cannot take strong or moderate inhibitors of CYP3A4. You should discuss your current medications with the trial team to ensure there are no interactions.
Is Abemaciclib generally safe for humans?
Abemaciclib has been studied in various cancers, including breast cancer and non-small cell lung cancer, and is generally considered safe with manageable side effects. Common side effects include diarrhea, infections, and neutropenia (low white blood cell count), with fatigue being a dose-limiting side effect. The maximum tolerated dose is 200 mg every 12 hours.
12345How is the drug Abemaciclib different from other treatments for Kaposi Sarcoma?
Abemaciclib is unique because it is a CDK4/6 inhibitor, which means it works by blocking proteins that help cancer cells grow and divide, a mechanism not typically used in treating Kaposi Sarcoma. This approach is different from other treatments that may not specifically target these proteins.
678910Eligibility Criteria
Adults over 18 with Kaposi Sarcoma (KS), either HIV-positive on effective therapy or HIV-negative, can join. They must have tried at least one KS treatment without success for phase 1, or not received any systemic therapy for phase 2b. Participants need good organ and marrow function, no severe infections, controlled hepatitis if present, and agree to use contraception.Inclusion Criteria
Your blood counts, liver function, and kidney function need to be within certain ranges. Your heart's pumping function also needs to be above a certain level.
Ability to understand and the willingness to sign a written informed consent document
I've been on ART for 8 weeks without KS improvement in the last 4 weeks.
+17 more
Exclusion Criteria
Participants who are receiving any other investigational agents
You have had serious allergic reactions to drugs similar to the CDK inhibitor.
I have recovered from side effects of previous cancer treatments, except for hair loss or nerve issues.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive abemaciclib in 28-day cycles until disease progression or unacceptable toxicity
Variable (until progression or toxicity)
1 visit per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Every 3 months for 6 months, then every 6 months for 2 years
Optional Extension
Participants with disease progression may receive an additional 12 weeks of treatment if deemed beneficial
12 weeks
Participant Groups
The trial is testing Abemaciclib's safety and effectiveness in shrinking KS tumors. It involves taking the drug orally every day in cycles of 28 days until cancer progression or unacceptable side effects occur. The study includes regular health checks, lesion assessments, quality of life questionnaires, and follow-ups for up to two years post-treatment.
3Treatment groups
Experimental Treatment
Group I: 2/Dose Expansion: Group 2bExperimental Treatment1 Intervention
Abemaciclib (at optimal dose determined in dose escalation portion of the study) for up to 10 previously untreated participants.
Group II: 2/Dose Expansion: Group 2aExperimental Treatment1 Intervention
Abemaciclib (at optimal dose determined in dose escalation portion of the study) for up to 15 participants previously treated with at least 1 line of systemic therapy.
Group III: 1/Dose Determination/De-EscalationExperimental Treatment1 Intervention
Abemaciclib (de-escalating dose)
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]Abemaciclib is an oral, selective small-molecule CDK 4 and 6 inhibitor. In preclinical models, abemaciclib synergized with programmed cell death protein-1 blockade to enhance antitumor efficacy. Here, we report the safety and anticancer activity of abemaciclib plus pembrolizumab in two cohorts with NSCLC.
First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.
Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. [2022]We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated dose was 200 mg every 12 hours. The most common possibly related treatment-emergent adverse events involved fatigue and the gastrointestinal, renal, or hematopoietic systems. Plasma concentrations increased with dose, and pharmacodynamic effects were observed in proliferating keratinocytes and tumors. Radiographic responses were achieved in previously treated patients with breast cancer, NSCLC, and melanoma. For hormone receptor-positive breast cancer, the overall response rate was 31%; moreover, 61% of patients achieved either response or stable disease lasting ≥6 months.
Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.
Abemaciclib: First Global Approval. [2019]Abemaciclib (Verzenio™) is an orally administered inhibitor of cyclin-dependent kinases 4 and 6 that is being developed by Eli Lilly and Company. Abemaciclib has been approved in the USA for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, in combination with fulvestrant in women with disease progression following endocrine therapy, and as monotherapy in adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. In addition, abemaciclib is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of abemaciclib leading to its first approval for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
Cutaneous adverse events during vemurafenib therapy. [2018]Vemurafenib, an oral agent that selectively targets the BRAF V600E mutation, has recently emerged as the mainstay of treatment in patients with BRAF-positive stage IV melanoma. A spectrum of cutaneous adverse events has been associated with vemurafenib, ranging from benign rashes to malignant side effects such as keratoacanthoma and squamous cell carcinoma.
Improved survival with vemurafenib in melanoma with BRAF V600E mutation. [2022]Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation.
Managing Side Effects of Vemurafenib Therapy for Advanced Melanoma. [2022]Somatic point mutations in the BRAF gene have been found in approximately 50% of melanomas. BRAF (V600E), the most common mutation, results in the constitutive activation of BRAF (V600E) kinase, sustaining MAPK signaling and perpetuating cell growth. This groundbreaking discovery led to the clinical development of vemurafenib, a selective BRAF inhibitor. Vemurafenib has been approved for the treatment of patients with BRAF (V600E)-positive unresectable or metastatic melanoma based on survival benefit demonstrated in a randomized phase III study. The current approved dosing schedule of vemurafenib is 960 mg orally twice a day until disease progression or unacceptable toxicity. Vemurafenib is well tolerated, with the most common adverse effects including skin reactions, photosensitivity, headache, and arthralgia. Active research is ongoing to expand the utility of vemurafenib into the adjuvant setting and to circumvent rapid emergence of drug resistance.
Response to targeted therapy in two patients with metastatic melanoma carrying rare BRAF exon 15 mutations: A598_T599insV and V600_K601delinsE. [2018]Concurrent BRAF-MEK inhibition improves clinical outcomes in patients with advanced BRAF V600E/K-mutant melanoma. There is currently less evidence for the efficacy of this treatment in patients with rare BRAF non-V600E/K genotypes. We report on two patients with rare BRAF exon 15 mutations - BRAF A598_T599insV and V600_K601delinsE - obtaining clinical benefit and a radiological response to inhibitors directed against the mitogen-activated protein kinase pathway. This highlights the importance of using tests that detect both V600E/K and non-V600E/K BRAF mutations to keep open the possibility of treatment with targeted therapy in patients with uncommon, yet potentially actionable, BRAF exon 15 mutations.
Selective BRAF inhibitors make inroads in mutated metastatic melanoma. [2019]The discovery that up to 50% of melanomas harbor mutations in the BRAF gene was made in 2002 and fueled the investigation into its mechanistic role as a driver mutation. BRAF mutations at the V600 position result in a constitutively active protein that underlies a classic "oncogene addiction." Since then, there have been extensive efforts to inhibit the mutated BRAF V600E/K as a therapeutic strategy. Initial attempts were made with either nonspecifc inhibitors of BRAF or with MEK inhibitors in studies that were not enriched for tumors with the BRAF mutation. The development of selective BRAF inhibitors that potently inhibit BRAF V600E/K and quench its downstream signaling revolutionized targeted therapy in melanoma. Vemurafenib was the first such agent and was developed in a phase 1 study that determined its maximally tolerated dose (MTD) to be 960 mg taken orally twice a day, and observed unprecedented tumor regression in more than 80% of patients. Those impressive results were confirmed in phase 2 and 3 studies (BRIM2 and BRIM3) and led to the drug's approval by the US Food and Drug Administration in 2011.