Cabozantinib + 177Lu-PSMA-617 for Prostate Cancer

(CaboLu Trial)

Overseen By Susan Sharry

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Utah

Must be taking: Androgen-deprivation therapy

Must not be taking: Anticoagulants, Anticancer agents

Disqualifiers: Brain metastases, Uncontrolled hypertension, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, phase 1b dose-escalation study of cabozantinib in combination with 177Lu-PSMA-617 in subjects with mCRPC. The primary hypothesis is that cabozantinib with 177Lu-PSMA will be safe and have efficacy in patients with mCRPC. The dose-escalation phase (Part 1) will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule for the subsequent expansion phase (Part 2).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions a washout period (time without taking certain medications) for prohibited medications before starting the treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Cabozantinib + 177Lu-PSMA-617 for prostate cancer?

Research shows that 177Lu-PSMA-617, a part of the treatment, is effective in treating metastatic castration-resistant prostate cancer, with 66% of patients experiencing a reduction in prostate-specific antigen levels, which is better than some chemotherapy options. ^{1 2 3 4 5}

What safety data exists for 177Lu-PSMA-617 in prostate cancer treatment?

177Lu-PSMA-617 has been studied for safety in treating metastatic castration-resistant prostate cancer, showing it is generally safe for use in humans. It targets prostate-specific membrane antigen (PSMA) on cancer cells, and while side effects are possible, they are typically explained by oncologists to patients. ^{1 2 4 5 6}

What makes the Cabozantinib + 177Lu-PSMA-617 treatment unique for prostate cancer?

This treatment combines Cabozantinib, a drug that inhibits cancer cell growth, with 177Lu-PSMA-617, a radiolabeled molecule that targets and delivers radiation directly to prostate cancer cells. This dual approach is novel because it combines targeted radiation with a drug that can potentially enhance the effectiveness of the radiation therapy. ^{1 2 3 6 7}

Research Team

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread. They must have had specific prior treatments, including hormone therapies and chemotherapy, show PSMA-positive lesions, be in good physical condition (ECOG ≤1), have proper organ function, and agree to use contraception. Excluded are those with certain severe illnesses or recent surgeries, uncontrolled hypertension, brain metastases not stable for 4 weeks, active infections like HIV or hepatitis B/C.

Inclusion Criteria

I am a man aged 18 or older.

Able to provide informed consent and willing to sign an approved consent form

Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception

Exclusion Criteria

Receiving other investigational anti-cancer agents

Medical, psychiatric, cognitive, or other conditions that may compromise study participation

I have been treated with cabozantinib before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule

4 weeks

Dose Expansion

Expansion Phase to assess identified MTD and schedule from Part 1

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 weeks

Treatment Details

Interventions

• Cabozantinib

Trial Overview The study is testing different doses of Cabozantinib combined with a radioactive drug called Lutetium-177 PSMA-617 on men with metastatic castration-resistant prostate cancer (mCRPC). It aims to find the highest dose patients can take without serious side effects (MTD) before expanding the trial.

Participant Groups

Group I: Dose Expansion Cohort (Part 2) Experimental Treatment 1 Intervention

Expansion Phase to assess identified MTD and schedule from Part 1.

Group II: Dose Escalation (Part 1) Experimental Treatment 1 Intervention

Part 1 will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule

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

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

177Lu-PSMA-617 therapy resulted in a significant decline in PSA levels in 69.30% of patients after the first treatment cycle, indicating its efficacy in treating metastatic castration-resistant prostate cancer (mCRPC).

The therapy was found to be safe, with no significant adverse events reported across 12 studies involving 508 cases, suggesting it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of the 177Lu-PSMA-617 therapy in the treatment of metastatic castration-resistant prostate cancer: A meta-analysis]. Zhang, H., Xin, P., Zhang, YX.[2022]

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 II trial, the novel radiopharmaceutical 177Lu-PSMA-617 demonstrated a significantly higher prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer, with 66% of patients showing a response compared to only 37% in those treated with chemotherapy (cabazitaxel).

This suggests that 177Lu-PSMA-617 may be a more effective treatment option than traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide Reduces PSA in mCRPC. [2021]

In a meta-analysis of 6 studies involving 201 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA-617 demonstrated a high efficacy, with 87% of patients showing any decrease in prostate-specific antigen (PSA) levels and 66% achieving a PSA decrease of more than 50%.

The treatment was found to be relatively safe, with the most common side effect being xerostomia (dry mouth) occurring in 77.1% of patients, but only 3% experiencing severe cases, indicating that 225Ac-PSMA-617 is a promising option with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. Ma, J., Li, L., Liao, T., et al.[2022]

In a preliminary study of 21 patients with de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) who refused standard treatments, 225Ac-PSMA-617 showed a significant anti-tumor effect, with 95% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and 86% achieving a decline of 50% or more.

The treatment was well tolerated, with the most common side effect being mild dry mouth in 94% of patients, suggesting that 225Ac-PSMA-617 could be a promising alternative therapy for mHSPC patients who decline standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. Sathekge, M., Bruchertseifer, F., Vorster, M., et al.[2023]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of the 177Lu-PSMA-617 therapy in the treatment of metastatic castration-resistant prostate cancer: A meta-analysis]. [2022]

2. 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]

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

Radionuclide Reduces PSA in mCRPC. [2021]

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

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]

7. 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]