November 17, 2020
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November 18, 2020
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May 16, 2024
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February 23, 2021
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December 31, 2024 (Final data collection date for primary outcome measure)
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- To evaluate safety and tolerability of docetaxel in combination with M9241 in patients who have metastatic prostate cancer. [ Time Frame: DLT observation period (until the end of 6 weeks) ]
of the number and type of toxicities noted for participants who are evaluable for toxicity
- Determine clinical efficacy in adults with prostate cancer treated with docetaxel in combination with the immunocytokine, M9241 [ Time Frame: 4-8 weeks ]
For castration sensitive: Increase in the proportion of participants who have less than 0.2 ng/ml of PSA. For castration resistant: Increase in median progression free survival
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- To evaluate safety and tolerability of docetaxel in combination with M7824 and M9241 in patients who have metastatic prostate cancer. [ Time Frame: DLT observation period (until the end of 6 weeks) ]
of the number and type of toxicities noted for patients who are evaluable for toxicity
- Determine clinical efficacy in adults with prostate cancer treated with docetaxel in combination with Anti-PD-L1/TGF-beta trap (M7824) and the immunocytokine, M9241 [ Time Frame: 4-8 weeks ]
For castration sensitive: Increase in the proportion of patients who have less than 0.2 ng/ml of PSA. For castration resistant: Increase in median progression free survival
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Same as current
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Not Provided
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Not Provided
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M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer
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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
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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.
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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:
Design:
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Interventional
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Phase 1 Phase 2
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Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Cancer Of Prostate
- Prostate Neoplasms
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- Drug: ADT
For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.
- Drug: Prednisone
For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.
- Drug: M7824
M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks.
- Drug: Docetaxel
Docetaxel 75mg/m^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.
- Drug: M9241
M9241 at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.
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- Experimental: 1/Dose Escalation
Docetaxel plus M9241 dose escalation with optional prednisone and ADT as part of SOC
Interventions:
- Drug: ADT
- Drug: Prednisone
- Drug: Docetaxel
- Drug: M9241
- Experimental: 2/Safety Run-in (no longer applies; removed before enrollment)
Docetaxel plus M9241 RP2D plus M7824 with optional prednisone and ADT as part of SOC
Interventions:
- Drug: ADT
- Drug: Prednisone
- Drug: M7824
- Drug: Docetaxel
- Drug: M9241
- Experimental: 3/mCSPC: Dose Expansion
Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC
Interventions:
- Drug: ADT
- Drug: Prednisone
- Drug: Docetaxel
- Drug: M9241
- Experimental: 4/mCRPC: Dose Expansion
Docetaxel plus M9241 RP2D with optional prednisone and ADT as part of SOC
Interventions:
- Drug: ADT
- Drug: Prednisone
- Drug: Docetaxel
- Drug: M9241
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Not Provided
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Recruiting
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86
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Same as current
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December 31, 2024
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December 31, 2024 (Final data collection date for primary outcome measure)
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- INCLUSION 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.
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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
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AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal
-- Hepatic function based on Child-Pugh Class: Participants with hepatic impairment must have Child-Pugh Class A or better
- 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.
EXCLUSION CRITERIA:
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Sexes Eligible for Study: |
Male |
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18 Years and older (Adult, Older Adult)
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No
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United States
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NCT04633252
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210001 21-C-0001
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Not Provided
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGAP. |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (ICF) |
Time Frame: |
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active. |
Access Criteria: |
Clinical data will be made available via subscription to BTRIS and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians. |
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National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
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Same as current
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National Cancer Institute (NCI)
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Same as current
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Not Provided
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Principal Investigator: |
Ravi A Madan, M.D. |
National Cancer Institute (NCI) |
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National Institutes of Health Clinical Center (CC)
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May 13, 2024
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