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

Trial Summary

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.

What data supports the effectiveness of the treatment Lu-PSMA-617 for prostate cancer?

Lu-PSMA-617 has been shown to be effective in treating prostate cancer, as it was approved by the FDA for patients with PSMA-positive metastatic castration-resistant prostate cancer. Clinical trials have demonstrated its ability to selectively target and kill cancer cells while sparing healthy tissue. ^{1 2 3 4 5}

Is the treatment with Cabazitaxel/Carboplatin vs Lu-PSMA-617 generally safe for humans?

Lu-PSMA-617 has been shown to be safe in patients with prostate cancer, as it delivers targeted radiation to cancer cells while sparing healthy tissue. Cabazitaxel, used in chemotherapy, has also been evaluated for safety in prostate cancer patients, though both treatments can have side effects. ^{1 2 3 4 6}

How is the drug combination of Cabazitaxel/Carboplatin and Lu-PSMA-617 unique for prostate cancer?

The drug combination of Cabazitaxel/Carboplatin and Lu-PSMA-617 is unique because Lu-PSMA-617 is a radiolabeled molecule that specifically targets prostate cancer cells by binding to the prostate-specific membrane antigen (PSMA) and delivering targeted radiation, which helps kill cancer cells while sparing healthy tissue. This approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to find out what treatment works best for participants with metastatic prostate cancer that are not responding to hormone treatment and docetaxel and are also Prostate-specific membrane antigen(PSMA) positive.

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

Eligibility Criteria

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

[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]

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]

References

1. England 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). [2021]

2. United States 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. [2023]

3. England 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Combination of 177Lu-PSMA-617 and External Radiotherapy for the Treatment of Cerebral Metastases in Patients With Castration-Resistant Metastatic Prostate Cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]