Cabazitaxel/Carboplatin vs Lu-PSMA-617 for Prostate Cancer

(CATCH-177 Trial)

Overseen By Pedro Barata, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Hormone-sensitive, Small cell, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 30 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to determine which is more effective for men with advanced prostate cancer that hasn't responded to hormone treatment and the chemotherapy drug docetaxel. Participants will receive either a combination of the chemotherapy drugs cabazitaxel (Jevtana) and carboplatin or a different drug called Lu-PSMA-617. The study seeks participants whose prostate cancer has spread and who have specific markers identified through imaging, as well as those who have previously tried certain treatments without success. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to explore new options.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on any other investigational agents and should be on a stable dose of any bone-targeting therapy for at least 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining cabazitaxel and carboplatin yields better results for patients with advanced prostate cancer than using cabazitaxel alone. Studies have found that this combination is generally well-tolerated, though some patients may experience side effects. Common side effects include low blood counts, tiredness, and nausea, but proper medical care can often manage these.

For Lu-PSMA-617, research indicates it is an effective treatment with a low risk of serious side effects. Patients have reported less pain and positive responses, both in how they feel and in medical scans. Long-term safety data supports its use, though some patients might experience mild to moderate side effects, such as dry mouth or nausea.

Overall, both treatments have been thoroughly studied and appear to be safe options for treating prostate cancer, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle prostate cancer. Cabazitaxel and carboplatin are used together to combine the cell-killing power of chemotherapy with the platinum-based drug's ability to damage cancer cell DNA. On the other hand, Lu-PSMA-617 is a novel approach that delivers targeted radiation directly to prostate cancer cells by binding to a protein called PSMA, often found in high amounts on these cells. This targeted mechanism could potentially reduce side effects compared to traditional treatments like hormone therapy or broader-spectrum chemotherapy. These innovative approaches provide hope for more effective and tolerable treatment options for patients with prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic prostate cancer?

In this trial, participants will be assigned to one of two treatment arms. Arm 1 combines Cabazitaxel and Carboplatin. Previous studies have shown that adding Carboplatin to Cabazitaxel yields better results for treating advanced prostate cancer than using Cabazitaxel alone. This combination has helped about one-third of patients, who did not respond to Cabazitaxel alone, experience a drop in their prostate-specific antigen (PSA) levels, indicating treatment effectiveness.

Arm 2 involves Lu-PSMA-617, a treatment that targets cancer cells with radiation. Lu-PSMA-617 has shown promising results, with links to less pain and fewer side effects. Patients receiving Lu-PSMA-617 have demonstrated good survival rates, with many completing several rounds of treatment. Both treatments in this trial offer hope for those with advanced prostate cancer who have not responded to standard therapies. ^{1 4 6 7 8}

Who Is on the Research Team?

Pedro Barata, MD, MSc

Principal Investigator

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center Seidman Cancer Center, Cleveland Clinic Taussig Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that has spread and isn't responding to hormone therapy or docetaxel. Participants must have tumors that are PSMA positive, indicating a specific protein is present on their cancer cells.

Inclusion Criteria

My prostate cancer is resistant to hormone therapy and has spread, but I've been treated with hormone blockers.

I have been on a stable dose of bone-targeting therapy for at least 14 days.

I am older than 18 years.

Exclusion Criteria

I do not have any serious illnesses that are not under control.

I haven't had a serious cancer diagnosis other than skin cancer or superficial bladder cancer in the last 2 years.

I have had treatment for brain metastases before joining this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Cabazitaxel and Carboplatin or 177Lu-PSMA-617 based on their assigned arm

30 weeks

10 visits (in-person) for Cabazitaxel and Carboplatin arm, 6 visits (in-person) for 177Lu-PSMA-617 arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Carboplatin
• Lu-PSMA-617

Trial Overview The study compares two treatments: one group receives Cabazitaxel with Carboplatin, while the other gets an experimental treatment called Lu-PSMA-617. The goal is to determine which treatment works best for this type of cancer.

How Is the Trial Designed?

Group I: Arm 2: Lu-PSMA-617 Experimental Treatment 1 Intervention

Participants will receive 177Lu-PSMA-617 7.4 GBq IV on Day 1 (+/-1 week) of each 6-week cycle for up to 6 cycles or until disease progression, unacceptable toxicity

Group II: Arm 1: Cabazitaxel and carboplatin Experimental Treatment 1 Intervention

Cabazitaxel: Participants will receive cabazitaxel 20 mg/m2 as a one-hour intravenous infusion every three weeks for a total of 10 cycles or until disease progression, unacceptable toxicity. Carboplatin: Participants will receive carboplatin AUC 4 mg/mL/min every three weeks for a total of 10 cycles or until disease progression, unacceptable toxicity

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

In a phase 2 trial involving 200 men with metastatic castration-resistant prostate cancer, [177Lu]Lu-PSMA-617 showed a significantly higher prostate-specific antigen (PSA) response rate (66%) compared to cabazitaxel (37%), indicating its greater efficacy as a treatment option.

Patients receiving [177Lu]Lu-PSMA-617 experienced fewer severe adverse events (33%) compared to those on cabazitaxel (53%), suggesting a better safety profile for the radiolabeled therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Hofman, MS., Emmett, L., Sandhu, S., et al.[2023]

The TheraP trial is a phase 2 study comparing the safety and efficacy of cabazitaxel chemotherapy with 177 Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel, involving 200 patients.

177 Lu-PSMA-617 is being evaluated as a potentially life-prolonging treatment option, with the trial aiming to provide the first randomized evidence on its effectiveness compared to cabazitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TheraP: a randomized phase 2 trial of 177 Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603). Hofman, MS., Emmett, L., Violet, J., et al.[2021]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

In a phase 2 trial involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer, the PSMA inhibitor [177Lu]Lu-PSMA-617 showed comparable overall survival (OS) to docetaxel, with a median OS of 15.0 months for both treatments in intention-to-treat analysis.

The per-protocol analysis indicated a median OS of 19.0 months for [177Lu]Lu-PSMA-617 compared to 15.0 months for docetaxel, suggesting that [177Lu]Lu-PSMA-617 may offer improved outcomes when administered earlier in treatment, although no significant differences were found between the two therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2023]

Citations

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Real world outcomes with cabazitaxel (cab) plus ... This is the first study showing that the addition of car in those not responding to cab can recapture PSA response in roughly one third of patients.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31515154/

Cabazitaxel plus carboplatin for the treatment of ... - PubMed Interpretation: Carboplatin added to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1558767323002823

Combined Cabazitaxel and Carboplatin Treatment of ... In this study we showed that patients with PSA progression during cabazitaxel monotherapy could benefit from the addition of carboplatin to cabazitaxel.

4. yalemedicine.org yalemedicine.org/clinical-trials/s2312-testing-whether-the-addition-of-carboplatin-chemotherapy-to-cabazitaxel-chemotherapy-will-imp

A Phase III Study of Cabazitaxel With or Without ... Giving carboplatin with the standard of care chemotherapy drug cabazitaxel may be better at treating metastatic castrate-resistant prostate cancer.

5. swog.org swog.org/patients/trials-open-patients/combining-cabazitaxel-and-carboplatin-treat-castrate-resistant

Combining Cabazitaxel and Carboplatin to Treat Castrate- ... Previous studies showed that treatment with cabazitaxel and carboplatin may work better than cabazitaxel in patients with AVPC. This trial will ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12310731/

The efficacy and safety of cabazitaxel in the treatment of ... The results of this study indicate that CAB is an effective and relatively safe treatment in mCRPC, and TDM can maximize its therapeutic effects ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)33517-1/pdf

Safety Data of Cabazitaxel (JEVTANA®) in Patients ... The PSA decrease ≥50% was observed in 64% (31pts) and the median number of cycles administered was 6 at last check. Median progression free survival was 4.4 ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30408-5/abstract

Cabazitaxel plus carboplatin for the treatment of men with ... Carboplatin added to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant ...