Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Carcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Infective Agents

Anticoagulants

Bone Density Conservation Agents

Amino Acids

Gallium 68 PSMA-11

Pluvicto

Carbamide Peroxide

Edetic Acid

Pentetic Acid

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Chelating Agents

Calcium

Calcium, Dietary

Radiopharmaceuticals

Lysine

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Computed Tomography

Gallium Ga 68 Gozetotide

Lutetium Lu 177 Vipivotide Tetraxetan

Positron Emission Tomography

PSMA PET Scan

Questionnaire Administration

Single Photon Emission Computed Tomography

Stephanie Lira

Jeremie Calais

The randomized phase 2 FLEX MRT compares a group of patients treated with LuPSMA on a flexible and extended dosing schedule including "treatment holiday" periods (investigational arm, up to 12 cycles) to a control group treated with a fixed dosing schedule of 6 treatments cycles maximum administered every 6 weeks.

The flexible dosing schedule in the investigational arm, will be based on SPECT/CT response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on PET/CT every 12 weeks.

PRIMARY OBJECTIVE:

I. To assess a potential survival benefit (2-year survival rate) of patients treated with Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) therapy on a flexible dosing schedule including up to 12 cycles and potential "treatment holiday" periods in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatment cycles every 6 weeks.

SECONDARY OBJECTIVES:

I. To determine the safety of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

II. To compare the overall survival (OS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

III. To compare the progression-free survival (PFS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

IV. To compare the disease control rate (DCR) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

V. To compare the impact on bone pain level of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

VI. To compare the impact on health-related quality of life of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

EXPLORATORY OBJECTIVE:

I. To determine the dosimetry in organs and tumor lesions of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68 gozetotide (68Ga-PSMA-11) IV and undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) throughout the trial. Patients also undergo single photon emission computed tomography (SPECT)/CT, PET/CT, or CT on the trial.

ARM II: Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Upon completion of study treatment, patients are followed up every 3 months for 24 months from after first cycle of study treatment.

Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)

A Phase 2 Randomized Trial in Patients With Metastatic Castration Resistant Prostate Cancer to Determine the Efficacy of a Flexible Dosing Schedule of Lu-PSMA Treatment up to 12 Cycles Including Potential Treatment Holiday Periods in Comparison to the Standard Fixed Dosing Schedule of Six Cycles Every Six Weeks (FLEX-MRT)

Will be assessed patients treated with 177Lu-PSMA-617 therapy on a flexible dosing schedule (investigational arm) in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatments cycles every 6 weeks (control arm). Will be reported using descriptive statistics by means of number and percentage of patients dead 24 months after the first cycle.

Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE). Descriptive statistics (number and percentage) will be reported separately for adverse events (AE) in total and serious adverse events (SAE) based on CTC. These descriptive statistics will be presented for the whole treatment as well as separate for each cycle. In addition, the relationship of AE to the study drug (related, not related) will be reported. Both results from laboratory test, physical examinations and patients surveys will be included. Distribution of each result will be compared between both groups using appropriate tests (e.g., Mann-Whitney U test).

Group comparisons performed using appropriate tests including survival analyses (Kaplan-Meier estimator). Descriptive analyses (median, standard deviation) is used.

Group comparisons performed using appropriate tests including survival analyses (Kaplan-Meier estimator). Descriptive analyses (median, standard deviation) is used. Radiographic progression defined as the date of progression on single photon emission computed tomography (SPECT) by visual increase in tumor volume ≥ 30% compared to baseline ± new sites of disease and/or new sites of prostate-specific membrane antigen (PSMA)-negative disease progression on diagnostic computed to computed tomography (CT) or on PSMA positron emission tomography (PET)/CT. Prostate specific antigen (PSA) progression is the date when a ≥ 25% increase in PSA and an increase of 2 ng/mL or more from the nadir is documented and confirmed by a second consecutive value obtained 3 or more weeks later. Clinical progression defined as marked escalation in cancer related pain, immediate need for initiation of new anticancer treatment, and marked deterioration in Eastern Cooperative Oncology Group (ECOG) performance.

Will be defined as the proportion of patients achieving radiographic stable disease (SD), partial response (PR) or complete response (CR). CR is defined as absence of PSMA-avid tumor on either imaging modality. On SPECT/CT, PR is defined as a \> 30% reduction in visual tumor volume at all sites of involved disease compared to baseline cycle #1, no new sites of PSMA-avid tumor and no new sites of PSMA-negative tumor on diagnostic CT, and SD is defined as no change \> 30% in visual tumor volume compared to baseline cycle #1, no new sites of PSMA-avid tumor and no new sites of PSMA-negative tumor on diagnostic CT. Respective response groups on PSMA PET/CT are defined by Response Evaluation Criteria in Prostate-specific membrane antigen PSMA PET/CT criteria. Descriptive analysis will be used to determine the DCR.

Will be defined as PSA decline ≥ 50% or radiographic PR/CR as defined above. Descriptive analysis will be used to determine the DCR.

Descriptive analysis will be used to evaluate the impact on bone pain level by determining the proportion of patients with pain response defined by improvement from baseline (all patients with ≥ 4/10) of at least 2-point absolute improvement without an overall increase in opiate use.

As measured by Eastern Cooperative Oncology Group (ECOG) performance status scale (minimum 0, maximum 5, with higher scores meaning a worse outcome)

Will be reported using the Brief Pain Inventory - Short Form patient reported outcome questionnaire (9 questions including scales; minimum 0, maximum 10, with higher scores meaning a worse outcome).

Will be reported using the Functional Assessment of Cancer Therapy - Radionuclide Therapy patient reported outcome questionnaire (15 questions; minimum 0, maximum 5, with higher scores meaning a worse outcome).

Jonsson Comprehensive Cancer Center

Adenocarcinoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dermatologic Agents

Dexamethasone

Cyclophosphamide

Dexamethasone acetate

BB 1101

Ichthammol

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Patients receive cyclophosphamide PO QD and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Selina Laqui

Rashmi Verma, MD

This phase I trial tests the safety and side effects of cyclophosphamide given together with dexamethasone in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving low doses of cyclophosphamide daily may reduce side effects. Dexamethasone is a corticosteroid drug that is used to treat some of the problems caused by chemotherapy treatment. The combination of cyclophosphamide and dexamethasone may work better in treating patients with castration resistant prostate cancer.

PRIMARY OBJECTIVES: I. To evaluate the feasibility of using the combination of oral metronomic cyclophosphamide and oral dexamethasone for treatment of men with metastatic castration -resistant prostate Cancer (mCRPC) who have progressed on 2 or more prior treatments. II. To assess the safety of cyclophosphamide + dexamethasone in men with mCRPC who have progressed on 2 or more prior treatments. SECONDARY OBJECTIVE:I. To evaluate prostate specific antigen (PSA) response and progression free survival and time to event outcome in participants with mCRPC treated with cyclophosphamide and dexamethasone. EXPLORATORY OBJECTIVE: I. To analyze serial blood samples for PSA monitoring and tumor tissue for pRb (encoded by the RB1 gene) and p53 (encoded by the TP53 gene) mutations. OUTLINE: Patients receive cyclophosphamide orally (PO) once daily (QD) and dexamethasone PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer

A Phase I Study of Oral Metronomic Dosing of Oral Cyclophosphamide With Dexamethasone for Metastatic Castration Resistant Prostate Cancer

Feasibility, defined as \>= 80% of participants completing treatment, and safety as defined by Grade 3 or higher adverse events (AEs) observed per National Cancer Institute (NCI) Common Terminology Criteriafor Adverse Events (CTCAE 5.0) criteria

Number of participants experiencing adverse events (AEs), both non treatment related and treatment related, classified by severity and graded.

Defined as a decline in PSA of 50% or greater, confirmed evaluation every 28 days with no evidence of clinical progression or disease progression on imaging, consistent with previous definitions by the Prostate Cancer Working Group 2 (PCWG2). The PSA response rate will be estimated along with an exact 95% confidence interval. Kaplan-Meier analysis will be used to depict time-to-event outcomes graphically and estimate medians with 95% confidence intervals.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)	NCT06216249	Prostate Carcin... Stage IVB Prost...	Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... PSMA PET Scan Questionnaire A... Single Photon E...	18 Years -	Jonsson Comprehensive Cancer Center
Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)	NCT06216249	Prostate Carcin... Stage IVB Prost...	Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... PSMA PET Scan Questionnaire A... Single Photon E...	18 Years -	Jonsson Comprehensive Cancer Center
Cyclophosphamide and Dexamethasone for the Treatment of Metastatic Castration Resistant Prostate Cancer	NCT05479578	Castration-Resi... Metastatic Pros... Stage IVB Prost...	Cyclophosphamid... Dexamethasone	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for stage ivb prostate cancer american joint committee on cancer (ajcc) v8