M9241 + Docetaxel for Prostate Cancer

Overseen By Amy R Hankin, P.A.-C

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Anti-androgens

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: HIV, Autoimmune diseases, Hypertension, others

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks for mCSPC, variable for mCRPC

86 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse. Objective: To learn if giving docetaxel with M9241 is safe and effective for men with prostate cancer. Eligibility: Men age 18 and older with mCSPC or mCRPC. Design: Participants will be screened with a medical history and physical exam. Their diagnosis will be confirmed. Their symptoms and how well they do their normal activities will be reviewed. They will have blood and urine tests. Their heart will be evaluated. They will have imaging scans of the chest, abdomen, and pelvis. They will have bone scans with intravenous (IV) injections of Tc99 to check for tumor spread in the bones. Some screening tests will be repeated during the study. Participants may have tumor biopsies. Participants will get treatment in cycles. Each cycle will last 21 days. They will get docetaxel through IV infusion. They will get M9241 as an injection under the skin. Participants with mCSPC will have up to 6 cycles. Those with mCRPC will be treated until they cannot tolerate the side effects or their disease gets worse. Participants will have a follow-up visit 30 days after treatment ends. Those with mCSPC will then have follow-up visits at the clinic every 3 months.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as those for urinary symptoms like finasteride and dutasteride, and any drugs that affect PSA levels. You also cannot use medications that interact with specific liver enzymes (CYP3A4 and CYP2D6) within 14 days before starting the trial.

What data supports the effectiveness of the drug M9241 + Docetaxel for prostate cancer?

Research shows that Docetaxel, a component of the treatment, significantly improves survival in men with advanced prostate cancer that no longer responds to hormone therapy. It has been shown to work well when combined with other treatments, suggesting potential benefits when used with M9241. ^{1 2 3 4 5}

Is the combination of M9241 and Docetaxel safe for treating prostate cancer?

Docetaxel, also known as Taxotere, has been shown to be safe in various studies when used for prostate cancer, even in combination with other treatments like radiation therapy and androgen-deprivation therapy. However, adverse events are common, and safety data specific to the combination with M9241 (NHS-IL12) is not provided in the available research. ^{1 2 6 7 8}

What makes the drug M9241 + Docetaxel unique for prostate cancer treatment?

The combination of M9241 and Docetaxel is unique because it pairs a novel agent, M9241, with Docetaxel, a chemotherapy drug known to improve survival in advanced prostate cancer. This combination aims to enhance the anticancer effects by potentially targeting different mechanisms in the cancer cells, offering a new approach compared to standard treatments. ^{1 2 3 5 9}

Research Team

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for men aged 18+ with metastatic prostate cancer, either castration sensitive or resistant. They must have good organ function and performance status, resolved prior therapy toxicities to a mild level, and agree to use contraception. Men previously treated with certain anti-androgens are eligible unless they've had recent disease progression on docetaxel.

Inclusion Criteria

- PT <= 1.5 x ULN

- Hemoglobin >9 g/dL

I am a man aged 18 or older.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study

I have received docetaxel for metastatic castration-resistant prostate cancer.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive docetaxel and M9241 in cycles of 21 days. mCSPC participants receive up to 6 cycles, while mCRPC participants continue until progression or unacceptable toxicity.

18 weeks for mCSPC, variable for mCRPC

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. mCSPC participants have follow-up visits every 3 months.

3 months for mCSPC, variable for mCRPC

Every 3 months (in-person) for mCSPC

Dose Escalation

M9241 dose is escalated from a starting dose of 12 mcg/kg to 16.8 mcg/kg along with docetaxel to ensure safety before larger participant enrollment.

Variable

Treatment Details

Interventions

• Docetaxel
• M9241

Trial Overview The study tests the safety and effectiveness of M9241 combined with docetaxel in treating advanced prostate cancer. Participants will receive cycles of treatment; those with sensitive cancer get up to 6 cycles, while those resistant continue until side effects become intolerable or their disease worsens.

Participant Groups

Group I: 4/mCRPC: Dose Expansion Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC

Group II: 3/mCSPC: Dose Expansion Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC

Group III: 2/Safety Run-in (no longer applies; removed before enrollment) Experimental Treatment 5 Interventions

Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC

Group IV: 1/Dose Escalation Experimental Treatment 4 Interventions

Docetaxel plus M9241 dose escalation with optional prednisone and ADT as part of SOC

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

In a study of 47 men with metastatic castration-resistant prostate cancer (mCRPC), combining androgen deprivation therapy (ADT) with docetaxel chemotherapy (DTX) significantly improved radiographic progression-free survival (rPFS) compared to DTX alone, with median rPFS of 9.0 months versus 6.0 months.

While overall survival (OS) was similar between the two groups (42.0 months for DTX+ADT and 38.0 months for DTX), the study indicates that concurrent ADT with DTX is a beneficial strategy for improving disease control in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Jang, HS., Koo, KC., Cho, KS., et al.[2018]

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

In an updated analysis of the TAX 327 study involving 1,006 men with metastatic hormone-resistant prostate cancer, docetaxel administered every 3 weeks (D3P) showed a significant survival benefit compared to mitoxantrone (MP), with a median survival of 19.2 months for D3P versus 16.3 months for MP.

The survival advantage of D3P persisted across various patient subgroups, including age and baseline pain status, indicating its efficacy as a treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. Berthold, DR., Pond, GR., Soban, F., et al.[2022]

The combination of docetaxel (DTX) and the mTOR inhibitor temsirolimus (TEM) significantly enhances the anticancer effect in castration-resistant prostate cancer (CRPC) cells by inducing apoptosis and suppressing autophagy, with a 34% greater reduction in cell proliferation compared to higher doses of DTX alone.

In vivo studies showed that this combination treatment resulted in a 72% reduction in tumor growth after 14 days, indicating a promising strategy for improving chemotherapy outcomes in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells. Inamura, SO., Ito, H., Taga, M., et al.[2019]

In a Phase I study involving 18 patients with high-risk prostate cancer, the addition of weekly docetaxel chemotherapy at a safe dose of 20 mg/m² to high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) was found to be safe, with no severe toxicities reported.

At a median follow-up of 2.2 years, the treatment resulted in a high biochemical progression-free survival rate of 94%, indicating promising efficacy for this triple-therapy regimen in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. Chen, RC., Rosenman, JG., Hoffman, LG., et al.[2019]

In a pilot study of 15 patients with hormone-refractory prostate cancer resistant to paclitaxel-based chemotherapy, docetaxel (DTX) showed activity, with 33.3% of patients experiencing a 50% or greater reduction in prostate-specific antigen levels.

Despite its effectiveness, DTX treatment was associated with significant toxicities, including severe anemia in 66.7% of patients, highlighting the need for further research to optimize treatment regimens and manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. Urakami, S., Yoshino, T., Kikuno, N., et al.[2018]

Combining naftopidil with docetaxel (DTX) significantly enhances the inhibition of prostate cancer cell growth and induces more apoptosis in LNCaP and PC-3 cancer cells compared to DTX alone, as shown in animal models.

The study indicates that naftopidil not only adds to the effectiveness of DTX but also exhibits a synergistic effect, suggesting that this combination could lead to better clinical outcomes for patients with castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells. Ishii, K., Matsuoka, I., Kajiwara, S., et al.[2018]

Docetaxel has shown significant effectiveness as a single agent in treating hormone refractory prostate cancer, achieving a 42% prostate-specific antigen response rate in four phase-II studies.

Combining docetaxel with estramustine may enhance the response rate, but it also increases the risk of toxicity, and further evaluation in ongoing phase-III studies will clarify its overall role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]. Wolff, JM.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. [2018]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. [2018]

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

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. [2019]

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

Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer]. [2018]