M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer

Prostate Neoplasms Clinical Trial

Official title: A Phase I/II Study of M9241 With Docetaxel and Abiraterone in Adults With Metastatic Castration Sensitive and M9241 With Docetaxel in Castration Resistant Prostate Cancer

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

Background:

• A phase III trial demonstrated that combining docetaxel and androgen deprivation therapy (ADT) significantly improved survival (57.6 vs 44.0 months (hazard ratio HR=0.56, (0.44- 0.70), p <0.0001) for men with metastatic castration sensitive prostate cancer (mCSPC). The greatest benefit was seen in men with high volume disease (visceral disease or 4+ bone lesions with at least one beyond the pelvis and spine.)

• Docetaxel has limited efficacy in metastatic castration resistant prostate cancer (mCRPC) patients who have already progressed on anti-androgen therapy (abiraterone or enzalutamide).

• Intensification of treatment in de novo mCSPC patients by adding abiraterone to docetaxel and ADT has been shown in a phase III trial to significantly improve OS (0.82, (0.69 - 0.98) p=0 (Summation)030) and rPFS (HR=0.54,(0.41-0.71) p <0.0001)

• Clinical data have indicated that PSA <=0.20 ng/ml eight months after starting androgen deprivation therapy (ADT) is prognostic for overall survival based on data from the phase III trial.

• Preclinical data demonstrates that docetaxel increases uptake of M9241, an IL-12 immunocytokine that targets necrosis.

• Additional preclinical data demonstrates the potential anti-tumor synergy of M9241 when combined with docetaxel.

Objectives:

Phase I:

To evaluate safety and tolerability of docetaxel in combination with M9241 in participants who have metastatic prostate cancer.

Phase II:

-Determine clinical efficacy in adults with prostate cancer treated when standard of care is combined with M9241. For mCSPC the standard of care is docetaxel + abiraterone. For mCRPC the standard of care is docetaxel.

• For mCSPC participants: Clinical efficacy will be measured by prostate specific antigen (PSA <0.2 ng/ml) eight months after start of androgen deprivation therapy (ADT).

• For mCRPC participants: Clinical efficacy will be measured by an increase in their median progression free survival (PFS).

Eligibility:

• Men age >=18 years

• Histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist s report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

• Participants must have metastatic disease

• mCSPC participants must be within 134 days of starting ADT.

• mCRPC participants must have been previously treated with ADT.

Design:

• Open-label, single-center, non-randomized Phase I/II study

• To ensure safety of the combination before using in larger numbers of mCSPC and mCRPC participants, M9241 will be escalated from a starting dose of 12 mcg/kg and a second dose level of 16.8 mcg/kg along with docetaxel. mCSPC participants will receive a maximum of 6 cycles. mCRPC participants will continue until progression or unacceptable toxicity.

• The remaining participants will be enrolled onto the trial in the following expansion cohorts, each of which will receive the determined safe dose of M9241. ADT will be maintained/given per standard of care throughout the study.

• mCSPC participants: Once ADT established, simultaneous docetaxel 75 mg/m^2 (given every 3 weeks x 6 cycles starting at Cycle 1), with M9241 at the RP2D, given every 3 weeks from cycle 2 through cycle 6). Abiraterone will be given in addition to docetaxel from the start of cycle 1 at a dose of 1000mg by mouth once daily. Prednisone will be given orally at 5 mg twice a day and will not be optional.

• The first 6 participants in the mCSPC arm including abiraterone will be evaluated as a safety lead-in of M9241 at 12 mcg/kg. If there are 2 or more DLTs within these initial 6, then the doses will be de-escalated and 6 additional participants will be evaluated at this lower dose of M9241 at 8 mcg/kg.

• mCRPC participants: docetaxel 75 mg/m^2 (given every 3 weeks starting at Cycle 1) with M9241 at the RP2D, given every 3 weeks from cycle 2 onwards until disease progression or unacceptable toxicity. Prednisone will be given 5 mg twice a day for each dose or 10 mg once a day.

• It is anticipated that approximately 4 years may be required for accrual of up to 80 participants. ;

Related Conditions & MeSH terms

• Cancer Of Prostate
• Prostate Neoplasms
• Prostatic Neoplasms

• NCT number: NCT04633252
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Amy R Hankin, P.A.-C
• Phone: (240) 858-3149
• Email: amy.hankin@nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 23, 2021
• Completion date: December 31, 2024