What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as Abemaciclib (a Cyclin-Dependent Kinase 4 and 6 inhibitor) and 177Lu-PSMA-617 (a radioligand therapy targeting the PSMA receptor), have distinct side effect profiles. Abemaciclib is known to cause neutropenia, diarrhea, and increased creatinine levels, with older patients needing careful monitoring for myelosuppression. On the other hand, 177Lu-PSMA-617 can lead to high-grade bone marrow suppression, dry mouth, and other serious treatment-emergent adverse effects. Both treatments require careful management to mitigate these side effects and ensure patient safety.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that are similar to abemaciclib and 177Lu-PSMA-617. Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, is similar to other CDK 4/6 inhibitors like palbociclib and ribociclib, which are used in the treatment of other cancers such as breast cancer. For radioligand therapy, the FDA has approved lutetium Lu 177 vipivotide tetraxetan (also known as 177Lu-PSMA-617) for the treatment of PSMA-positive metastatic castration-resistant prostate cancer. This therapy targets the PSMA receptor on tumor cells and delivers a radioactive component to destroy them. These approvals highlight the evolving landscape of targeted therapies in prostate cancer treatment.

What other types of research exist?

Promising novel alternatives to Abemaciclib and 177Lu-PSMA-617 for prostate cancer patients include: <ol> <li>Immunotherapy agents such as Pembrolizumab and Atezolizumab, which have shown clinical activity in mCRPC.</li> <li></li> </ol> Radiopharmaceuticals like Radium-223, which targets bone metastases. 3. Multitargeted kinase inhibitors such as Regorafenib, Cabozantinib, and Sorafenib, which have demonstrated some activity in advanced prostate cancer. 4. Chimeric Antigen Receptor (CAR) T-cell therapies targeting PSMA, which are under investigation for their potential efficacy in mCRPC.

← Back to Search

Kinase Inhibitor

Abemaciclib + Radioligand Therapy for Prostate Cancer (UPLIFT Trial)

Phase 1 & 2

Recruiting

Led By Vadim S Koshkin, MD

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years.

Patients must have adenocarcinoma histology.

Must not have

The patient has active systemic bacterial infection (requiring intravenous (IV) antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive). Screening is not required for enrollment.

Patients with prior radiation treatment to lungs or liver.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if taking abemaciclib before using 177Lu-PSMA-617 can better treat prostate cancer that has spread and doesn't respond to usual treatments. Abemaciclib slows down cancer growth, and 177Lu-PSMA-617 uses radiation to kill the cancer cells. 177Lu-PSMA-617 targets a specific protein in prostate cancer cells and has shown promising results in treating advanced prostate cancer.

Who is the study for?

Men aged 18+ with metastatic castration resistant prostate cancer that has progressed despite previous taxane-based chemotherapy can join. They must have adequate organ function, no small cell/neuroendocrine carcinoma, and not be on recent anti-cancer therapy or have serious concurrent conditions. HIV-positive individuals on effective treatment are eligible.

What is being tested?

The trial is testing the safety and effectiveness of abemaciclib followed by radioligand therapy with 177Lu-PSMA-617 in men with advanced prostate cancer. Abemaciclib is a kinase inhibitor aiming to stop cancer growth, while 177Lu-PSMA-617 targets and kills tumor cells.

What are the potential side effects?

Potential side effects include fatigue, nausea, diarrhea, low blood counts leading to increased infection risk or bleeding problems, liver issues, kidney impairment and possibly others depending on individual health conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am 18 years old or older.

Select...

My cancer is of the adenocarcinoma type.

Select...

My PET scan shows at least 3 areas with higher PSMA levels than my liver.

Select...

I can swallow pills.

Select...

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

Select...

I have been treated with a new hormone therapy like abiraterone.

Select...

I have undergone treatment to lower my testosterone due to cancer.

Select...

My prostate cancer has spread and is not responding to hormone therapy.

Select...

I've had taxane-based chemotherapy and recovered from its effects, except for possible hair loss or mild nerve damage.

Select...

My prostate cancer diagnosis was confirmed through a biopsy.

Select...

I am able to get out of my bed or chair and move around.

Select...

My hepatitis B virus load is undetectable with treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have any active infections requiring IV antibiotics or known viral infections like HIV or active hepatitis B or C.

Select...

I have had radiation treatment to my lungs or liver.

Select...

I am experiencing symptoms related to spinal cord pressure.

Select...

I have had severe side effects from previous radiation treatment.

Select...

I haven't had certain radioactive treatments or half-body radiation in the last 6 months.

Select...

My cancer is either small cell or neuroendocrine type.

Select...

I have been treated with CDK4/6 inhibitors before.

Select...

I have had PSMA-targeted radioligand therapy before.

Select...

I have a history of serious heart rhythm problems or sudden cardiac arrest.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in maximum standardized uptake value (SUVmax) across three lesions on gallium Ga 68 gozetotide (68Ga-PSMA-11) positron emission tomography (PET) scan (Part B)

Proportion of participants with DLTs (Part A)

Recommended phase 2 dose (Part A)

Secondary study objectives

Disease control rate (Part B)

Median duration of response (DOR) (Part B)

Median overall survival (OS) (Part B)

+4 more

Side effects data

From 2018 Phase 2 trial • 132 Patients • NCT02102490

91%

Diarrhoea

67%

Nausea

48%

Fatigue

45%

Decreased appetite

35%

Vomiting

27%

Anaemia

26%

Abdominal pain

23%

Asthenia

23%

Neutrophil count decreased

21%

Cough

20%

Constipation

20%

Headache

19%

Arthralgia

18%

White blood cell count decreased

18%

Neutropenia

15%

Alopecia

14%

Dry mouth

14%

Platelet count decreased

14%

Weight decreased

14%

Dysgeusia

13%

Dyspnoea

12%

Abdominal pain upper

12%

Back pain

12%

Dizziness

11%

Oedema peripheral

11%

Dyspepsia

11%

Pyrexia

11%

Blood creatinine increased

10%

Pain

Stomatitis

Aspartate aminotransferase increased

Thrombocytopenia

Lacrimation increased

Dehydration

Dry skin

Pruritus

Alanine aminotransferase increased

Flatulence

Upper respiratory tract infection

Urinary tract infection

Hypokalaemia

Chills

Musculoskeletal chest pain

Musculoskeletal pain

Anxiety

Gastrooesophageal reflux disease

Rash

Myalgia

Cellulitis

Pleural effusion

Atypical pneumonia

Gastroenteritis viral

Lung infection

Sepsis

Fall

Hip fracture

Pneumonitis

Pneumothorax

Febrile neutropenia

Respiratory tract infection

Haematotoxicity

Sinus bradycardia

Tachycardia

Large intestinal obstruction

Pancreatic enzyme abnormality

Pancreatitis

Varices oesophageal

Electrocardiogram abnormal

Liver function test abnormal

Renal function test abnormal

Bone pain

Muscular weakness

Acute kidney injury

Pulmonary embolism

Arterial thrombosis

Epilepsy

100%

80%

60%

40%

20%

Study treatment Arm

Abemaciclib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part B: Recommended Phase 2 dose of Abemaciclib, 177Lu-PSMA-617Experimental Treatment2 Interventions

Patients receive the recommended phase 2 dose of abemaciclib lead-in on days 1-14 and lutetium Lu 177 vipivotide tetraxetan IV over 30 minutes on day 15. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Part A: Abemaciclib, 177Lu-PSMA-617Experimental Treatment2 Interventions

Patients receive abemaciclib lead-in on days 1-14 and lutetium Lu 177 vipivotide tetraxetan IV over 30 minutes on day 15. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abemaciclib

2019

Completed Phase 2

~1890

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments work through various mechanisms to target and destroy cancer cells. Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, blocks proteins involved in cell growth and differentiation, thereby preventing cancer cell proliferation. 177Lu-PSMA-617, a radioligand therapy, targets the prostate-specific membrane antigen (PSMA) on tumor cells, delivering radiation directly to the cancer cells to destroy them. These treatments are crucial as they offer targeted approaches to manage and potentially reduce the spread of prostate cancer, improving patient outcomes and quality of life. Other common treatments include androgen receptor inhibitors like enzalutamide, which block the effects of androgens that fuel cancer growth, and chemotherapy agents like docetaxel, which kill rapidly dividing cells. Each treatment's mechanism of action is designed to disrupt cancer progression in different ways, providing multiple avenues for combating the disease.

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review.Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial.