RECRUITING

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

Conditions

Cancer Of Prostate Prostate Neoplasms Chemoimmunotherapy NHS IL-12 Check point inhibitor Combination Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2021-02-23

Study Completion:2026-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04633252

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participants must have documented 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, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1. * mCSPC participants: * Participants must be within 134 days of starting ADT. * If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases. * For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease. * For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis). * mCRPC participants: * Must need ADT as part of their cancer therapy (unless previous orchiectomy) * Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide. * Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC. * Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan. * Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to \<= grade 1. * Men age \>=18 years. Because no dosing or adverse event data are currently available on the use of M9241 in combination with docetaxel in participants \<18 years of age, children are excluded from this study. * ECOG performance status 0-2. * Participants must have adequate organ and marrow function as defined below: * Absolute neutrophil count \>=1,500/mcL, without CSF support * Platelets \>=100,000/mcL * Hemoglobin \>9 g/dL * PT \<= 1.5 x ULN * aPTT \<= 1.5 x ULN * Total bilirubin \<= upper limit of normal (ULN), OR in participants with Gilbert s syndrome, a total bilirubin \<= 3.0 * Serum albumin \>=2.8 g/dL * AST(SGOT)/ALT(SGPT) \<=1.5 X institutional upper limit of normal * Serum Creatinine OR Creatinine Clearance \<= 1.5 X institutional upper limits of normal OR \>=50 mL/min/1.73 m\^2 calculated by eGFR in the clinical lab for participants with serum creatinine levels \> 1.5 ULN * The effects of M9241 in combination with docetaxel and abiraterone on the developing human fetus are unknown. For this reason and because docetaxel agents as well as other immuno-therapeutic agents used in this trial are known to be teratogenic, sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom)after enrollment on study , during the study treatment and for 4 months after the last dose of abiraterone, docetaxel or M921, even if oral contraceptives are also used. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately and her partner should inform the study doctor immediately. * Ability of subject to understand and the willingness to sign a written informed consent document. Subject should be willing to travel to the NIH for follow-up visits. * Participants with prior immune checkpoint therapy are eligible to enroll upon PI discretion.	* Immunocompromised status due to: * Human immunodeficiency virus (HIV) positivity * Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed. * Other immunodeficiency diseases that in the opinion of the investigator could compromise the participants or limit treatment efficacy * Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with a participant s ability to carry out the treatment program. * Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto). * Concurrent use of CYP3A4 inducers or sensitive CYP2D6 substrates within 14 days or 5 half-lives, whichever is shorter. * Receipt of any investigational agent within 28 days (or 60 days for an antibody drug conjugates) before the first planned dose of study drugs. * Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody * Uncontrolled hypertension (SBP\>170/ DBP\>105) * Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted. * Participants who have had prior docetaxel for mCRPC * mCSPC participants will be excluded if they did not start abiraterone within 6 weeks of ADT and/or had any docetaxel * Participants who have had progression within 3 months of completing docetaxel for mCSPC * History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study * The subject has had evidence within 3 years of the start of study treatment of another active malignancy which required systemic treatment (except for nonmelanoma skin cancers or carcinoma in situ of the bladder). * The subject has active brain metastases or epidural disease. * Participants with greater than or equal to grade 2 peripheral neuropathy (defined by CTCAE 5.0) at baseline.

Inclusion Criteria

Exclusion Criteria

* Participants must have documented 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, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.
* mCSPC participants:
* Participants must be within 134 days of starting ADT.
* If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases.
* For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease.
* For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis).
* mCRPC participants:
* Must need ADT as part of their cancer therapy (unless previous orchiectomy)
* Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
* Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC.
* Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan.
* Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to \<= grade 1.
* Men age \>=18 years. Because no dosing or adverse event data are currently available on the use of M9241 in combination with docetaxel in participants \<18 years of age, children are excluded from this study.
* ECOG performance status 0-2.
* Participants must have adequate organ and marrow function as defined below:
* Absolute neutrophil count \>=1,500/mcL, without CSF support
* Platelets \>=100,000/mcL
* Hemoglobin \>9 g/dL
* PT \<= 1.5 x ULN
* aPTT \<= 1.5 x ULN
* Total bilirubin \<= upper limit of normal (ULN), OR in participants with Gilbert s syndrome, a total bilirubin \<= 3.0
* Serum albumin \>=2.8 g/dL
* AST(SGOT)/ALT(SGPT) \<=1.5 X institutional upper limit of normal
* Serum Creatinine OR Creatinine Clearance \<= 1.5 X institutional upper limits of normal OR \>=50 mL/min/1.73 m\^2 calculated by eGFR in the clinical lab for participants with serum creatinine levels \> 1.5 ULN
* The effects of M9241 in combination with docetaxel and abiraterone on the developing human fetus are unknown. For this reason and because docetaxel agents as well as other immuno-therapeutic agents used in this trial are known to be teratogenic, sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom)after enrollment on study , during the study treatment and for 4 months after the last dose of abiraterone, docetaxel or M921, even if oral contraceptives are also used. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately and her partner should inform the study doctor immediately.
* Ability of subject to understand and the willingness to sign a written informed consent document. Subject should be willing to travel to the NIH for follow-up visits.
* Participants with prior immune checkpoint therapy are eligible to enroll upon PI discretion.

* Immunocompromised status due to:
* Human immunodeficiency virus (HIV) positivity
* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
* Other immunodeficiency diseases that in the opinion of the investigator could compromise the participants or limit treatment efficacy
* Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with a participant s ability to carry out the treatment program.
* Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
* Concurrent use of CYP3A4 inducers or sensitive CYP2D6 substrates within 14 days or 5 half-lives, whichever is shorter.
* Receipt of any investigational agent within 28 days (or 60 days for an antibody drug conjugates) before the first planned dose of study drugs.
* Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody
* Uncontrolled hypertension (SBP\>170/ DBP\>105)
* Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
* Participants who have had prior docetaxel for mCRPC
* mCSPC participants will be excluded if they did not start abiraterone within 6 weeks of ADT and/or had any docetaxel
* Participants who have had progression within 3 months of completing docetaxel for mCSPC
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study
* The subject has had evidence within 3 years of the start of study treatment of another active malignancy which required systemic treatment (except for nonmelanoma skin cancers or carcinoma in situ of the bladder).
* The subject has active brain metastases or epidural disease.
* Participants with greater than or equal to grade 2 peripheral neuropathy (defined by CTCAE 5.0) at baseline.

Contacts and Locations

Study Contact

Amy R Hankin, P.A.-C

CONTACT

(240) 858-3149

amy.hankin@nih.gov

Ravi A Madan, M.D.

CONTACT

(301) 480-7168

rm480i@nih.gov

Principal Investigator

Ravi A Madan, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Ravi A Madan, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-23

Study Completion Date2026-12-31

Study Record Updates

Study Start Date2021-02-23

Study Completion Date2026-12-31

Terms related to this study

Keywords Provided by Researchers

Chemoimmunotherapy
NHS IL-12
Check point inhibitor
Combination Therapy

Additional Relevant MeSH Terms

Cancer Of Prostate
Prostate Neoplasms