Imifoplatin for Metastatic castration-resistant prostate cancer | Castration-resistant prostate cancer

Stratification factors

• Bone-only disease (yes vs. no)

Inclusion criteria

• {"criterion_text":"- Signed informed consent before initiation of any study-specific procedures and treatment;"}
• {"criterion_text":"- ECOG performance status of 0-1;"}
• {"criterion_text":"- Estimated life expectancy of ≥16 weeks."}
• {"criterion_text":"- Must have recovered to CTCAE grade ≤ 1 from all clinically significant toxicities related to prior cancer therapies, excluding alopecia or toxicities related to the use of LHRH agonist or antagonist, based on CTCAE v5.0;"}
• {"criterion_text":"- Adequate bone marrow, liver, and renal function."}
• {"criterion_text":"- Must use a condom during study treatment and 6 months after the last dose of PT-112 when having intercourse with a pregnant woman or a woman of childbearing potential. Female partners of male patients also should use a highly effective form of contraception if they are of childbearing potential."}
• {"criterion_text":"- The patient is willing and able to comply with the protocol for the study’s duration, including undergoing treatment and scheduled visits and examinations at the institution and completing required surveys, assessments, and follow-up visits."}
• {"criterion_text":"- Male ≥18 years of age;"}
• {"criterion_text":"- Histologically or cytologically confirmed adenocarcinoma of the prostate, excluding pure neuroendocrine/small-cell features at original diagnosis;"}
• {"criterion_text":"- Documented current evidence of metastatic castration-resistant prostate cancer (mCRPC), where metastatic status is defined as having documented metastatic lesion(s) on either bone scan or CT scan. Patients whose disease spread is limited to regional pelvic lymph nodes or local recurrence (e.g., bladder, rectum) are not eligible."}
• {"criterion_text":"- Ongoing androgen deprivation therapy with a GnRH analog or a bilateral orchiectomy (i.e., surgical or medical castration);"}
• {"criterion_text":"- Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at screening;"}
• {"criterion_text":"- Patients receiving bisphosphonates or denosumab must have been on a stable dose for at least 4 weeks before starting the study. No bisphosphonate treatment was administered within 7 days before initiating study treatment. While on the study, denosumab may be administered on the same day as PT- 112. However, bisphosphonates can be administered only once a month on Day 21 (±2 days) of the 28-day treatment cycle or, in the event of dose holds, can be given only 7 (±2) days apart from any PT-112 infusions."}
• {"criterion_text":"- Patients who have received at least three prior intended life-prolonging therapies for metastatic disease, as follows: a. At least one new-generation anti-androgen therapy (e.g. abiraterone, apalutamide, darolutamide, enzalutamide); b. At least one but no more than two taxane-containing regimens (e.g., docetaxel, cabazitaxel). Use of docetaxel in the mHSPC setting counts toward this number. Patients receiving the same taxane-containing regimen(s) at separate points in time during their course of therapy are considered to have received separate exposures; c. Other FDA approved therapy for mCRPC (e.g., including radium 223, sipuleucel-T, PARP inhibitors, 177Lutetium-PSMA-617) or other agents which may be approved during the conduct of this study based on a demonstrated treatment benefit on survival; d. Prior investigational regimens are allowed but do not count towards this number."}
• {"criterion_text":"- Progressive disease at study entry, defined as either / both of the following criteria that occurred on or after the most recent therapy (Note: for the avoidance of doubt, PSA progression alone does not fulfill this criterion): ● Soft-tissue disease progression, defined by RECIST v1.1. (Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible under this parameter); ● Bone disease progression, defined by PCWG3 as ≥ 2 new lesions confirmed on bone scan."}

Exclusion criteria

• {"criterion_text":"- Intolerance to CT, or FDG-PET contrast agents, as applicable."}
• {"criterion_text":"- History or current evidence of any circumstance, condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate in the opinion of the Investigator;"}
• {"criterion_text":"- Known hypersensitivity to platinum-containing therapies, PT-112, or any of PT-112 Injection excipients;"}
• {"criterion_text":"- Patients on therapeutic doses of anti-coagulants."}
• {"criterion_text":"- Target disease exceptions: a. Carcinomatous meningitis; b. Known brain metastases and/or active epidural disease, subject to the following exceptions: - Patients with a history of CNS metastases are eligible if they have received therapy if required (e.g., surgery, radiotherapy, gamma knife), are neurologically stable, asymptomatic, have no single lesion > 2 cm, and are not receiving corticosteroids to maintain neurologic integrity; - Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable (not requiring steroids for at least 28 days before the first dose of PT-112), and they have had appropriate scans at screening assessment. For patients with parenchymal and CNS metastasis or a history of CNS metastasis, baseline and subsequent radiologic imaging must include evaluation of the brain; - Patients with epidural disease, canal disease, and prior cord involvement are eligible if they are not neurologically impaired, those areas are stable, and symptoms are readily controlled. For these patients, baseline and subsequent radiologic imaging must include evaluation of the brain; c. Symptomatic or impending cord compression unless appropriately treated, clinically stable, and asymptomatic;"}
• {"criterion_text":"- Patients non-evaluable for both bone and soft-tissue progression, as defined by meeting both of the following criteria:A bone scan that is referred to as a superscan showing an intense symmetric activity in the bones; ● No soft tissue lesion (measurable or non-measurable) can be assessed by RECIST v1.1."}
• {"criterion_text":"- Any minor surgical procedure within <5 days or any major surgical procedure within <28 days before the first dose of PT-112. In all cases, patients must be sufficiently recovered and stable before starting PT-112 treatment;"}
• {"criterion_text":"- Received treatment with chemotherapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, radiation, experimental drug, or PARP inhibitors within < 14 days of receiving the first dose of PT-112. Treatment with hormonal therapies (except for LHRH analog) must be discontinued at least 14 days before the first dose of PT-112;"}
• {"criterion_text":"- Medical history and concurrent disease: a. Active infection requiring systemic therapy or significant acute or chronic infection including, among others: - Active hepatitis B virus (HBV) infection, defined by a positive HBV surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as the presence of hepatitis B core antibody and absence of HBsAg, are eligible; - Active hepatitis C virus (HCV) infection, defined by HCV RNA positive PCR test at screening; - Known history or testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;"}
• {"criterion_text":"- Resting ECG indicating uncontrolled cardiac condition, including unstable ischemia, uncontrolled asymptomatic arrhythmia, congestive heart failure (New York Heart Association functional classification Grade II or higher), or QTcF prolongation >450 ms, or patients with congenital long QT syndrome;"}
• {"criterion_text":"- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, superficial bladder cancer, and patients with a prior history of malignancy who have been disease-free for 3 years or more are eligible;"}
• {"criterion_text":"- Known psychiatric or substance abuse disorders that might interfere with cooperation with the requirements of the trial;"}

Primary endpoints

• {"endpoint_text":"- Expansion cohort D (metastatic Castration-Resistant Prostate Cancer): Define the recommended dose and schedule for PT-112 for pivotal studies, administered either as 250 mg/m2 on Days 1 and 15 of each 28- day cycle (Arm 2) or as 360 mg/m2 on Days 1 and 15 of Cycle 1, then 250 mg/m2 on Day 15 of each subsequent 28-day cycle (Arm 3), where the primary endpoint (benefit) is defined as DCR4.","definition_or_measurement_approach":"Primary endpoint defined as DCR4 (disease control rate at 4 months)."}

Secondary endpoints

• {"endpoint_text":"- ● Disease control rate (DCR) by disease manifestation","definition_or_measurement_approach":"DCR assessed by disease manifestation (per disease-specific assessments)."}
• {"endpoint_text":"- ● Objective response rate (ORR) in patients with RECIST-measurable disease, defined as the percentage of patients achieving a confirmed PR and CR, based on tumor assessments by CT with contrast at baseline and after every 2 cycles (8±1 weeks) of treatment through the first 6 months, then every 3 cycles (12±1 weeks), evaluated using PCWG3-modified RECIST criteria;","definition_or_measurement_approach":"ORR = % patients with confirmed PR or CR by CT with contrast using PCWG3-modified RECIST; assessments baseline, every 2 cycles (8±1 weeks) for first 6 months, then every 3 cycles (12±1 weeks)."}
• {"endpoint_text":"- ● The median duration of response (DOR) for soft tissue (non-bone) lesions, calculated as from the first observation of response to the first observation of disease progression using PCWG3-modified RECIST criteria;","definition_or_measurement_approach":"Median DOR calculated from first observation of response to first observation of progression using PCWG3-modified RECIST."}
• {"endpoint_text":"- ● Percentage of patients who are CTC nonzero at baseline and with 0 CTCs/mL in one or more post-baseline samples (i.e., CTC0);","definition_or_measurement_approach":"Proportion of patients with >0 CTC at baseline who achieve 0 CTCs/mL in ≥1 post-baseline sample."}
• {"endpoint_text":"- ● Percentage of patients who have ≥ 3 CTCs at baseline and ≤ 3 CTCs in one or more post-baseline samples (i.e., CTC conversion);","definition_or_measurement_approach":"Proportion of patients with ≥3 baseline CTCs who have ≤3 CTCs in ≥1 post-baseline sample."}
• {"endpoint_text":"- ● Percentage of patients achieving PSA50 defined as ≥ 50% reduction in serum PSA from Cycle 1 Day 1 that is confirmed at the start of a subsequent cycle as defined by PCWG3 criteria;","definition_or_measurement_approach":"PSA50 = ≥50% reduction in serum PSA from Cycle 1 Day 1 confirmed at start of subsequent cycle per PCWG3."}
• {"endpoint_text":"- ● Median radiographic progression-free survival (rPFS), calculated from the start of study drug to the first observation of radiographic disease progression by PCWG3 criteria;","definition_or_measurement_approach":"rPFS measured from first dose to first radiographic progression per PCWG3 criteria."}
• {"endpoint_text":"- ● Median overall survival (OS);","definition_or_measurement_approach":"OS measured as time from first dose to death from any cause (median)."}
• {"endpoint_text":"- ● Time to PSA progression by PCWG3 criteria, calculated from the start of study drug to the first observation of PSA progression by PCWG3 criteria;","definition_or_measurement_approach":"Time from first dose to first PSA progression per PCWG3 criteria."}
• {"endpoint_text":"- ● Change in disease-related pain, based on American Cancer Society Daily Pain Diary assessment of worst pain over the past 24 hours (11 point scale) and analgesic consumption","definition_or_measurement_approach":"Change in worst pain over past 24 hours (11-point scale) from ACS Daily Pain Diary and analgesic use."}
• {"endpoint_text":"- ● Number of treatment-related adverse events (TRAEs) as a measure of safety and tolerability;","definition_or_measurement_approach":"Count and characterization of treatment-related AEs (TRAEs) reported during study."}
• {"endpoint_text":"- ● Determine the pharmacokinetics of PT-112 following dosing on Days 1 and 15 of Cycle 1;","definition_or_measurement_approach":"PK sampling following dosing on Days 1 and 15 of Cycle 1 to determine PT-112 pharmacokinetic parameters."}
• {"endpoint_text":"- ● Assess exposure-response and exposure-safety relationships for PT-112.","definition_or_measurement_approach":"Exposure-response and exposure-safety analyses relating PT-112 exposure metrics to efficacy and safety outcomes."}

France

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

504

Number Of Sites

9

Number Of Participants

40

Primary sponsor

Full Name

Promontory Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Inc.

Responsibilities

sample storage; responsibilities indicated as code 4 in sponsorDuties

Third parties

• {"country":"United States","full_name":"Scisafe Inc.","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"sample storage; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPIC Sciences","duties_or_roles":"code 4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"sample storage; code 4","organisation_type":"Pharmaceutical company"}