BridgeMD
New treatment option for Aggressive Variant Prostate Carcinoma
Official title Zanzalintinib in Men With Aggressive Variant Prostate Cancer
ClinicalTrials.gov ID: NCT07218666
What this study is testing
What is Zanzalintinib?
Zanzalintinib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for aggressive variant prostate carcinoma.
Also referred to as XL092.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is a multi-center single arm phase II study to evaluate the antitumor activity of zanzalintinib 60mg orally (PO) once daily in subjects with AVPC. Zanzalintinib may continue until radiographic progression (or beyond), intolerable adverse events, or withdrawal of consent.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older, men only
You may be able to join if
- Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be...
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
- Histological or cytologically proven prostate cancer
- Must have had evidence of metastatic disease (AJCC v.8 M1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
You likely can't join if
- Pure small cell carcinoma of the prostate.
- Prior treatment with zanzalintinib.
- Imminent or established spinal cord compression based on clinical and/or imaging findings.
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study drug.
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of start of...
- Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study drug. Systemic...
See the full eligibility criteria
Who can join
- Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
- Histological or cytologically proven prostate cancer
- Must have had evidence of metastatic disease (AJCC v.8 M1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
- Bone metastases detected by CT, radionuclide 99Tc- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria, OR
- Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥15 mm) detected on CT or MRI as defined by RECIST version 1.1. people with...
- Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm.
- Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone \< 50 ng/ dL (\< 1.73 nmol/L) at...
- Must have progressed during or after at least one second-generation androgen receptor pathway inhibitor (abiraterone acetate, enzalutamide, apalutamide, darolutamide) given for castration-sensitive locally advanced (T3...
- Presence of at least one of the following:
- Presence of visceral metastases or high-volume disease (\> 4 sites of metastases) on conventional imaging (CT/MRI/bone scan) with a PSA ≤ 5.
- Predominantly lytic bone metastasis.
- Bulky (≥5 cm) lymphadenopathy OR bulky (≥5 cm) high-grade (Gleason ≥8) tumor mass in the prostate/pelvis.
- Serum chromogranin A level ≥ 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2× ULN.
- Prostate adenocarcinoma with IHC staining for neuroendocrine markers (positive staining of chromogranin A or synaptophysin).
- Alterations in at least two of the three tumor suppressor genes: TP53, RB1 and PTEN on genomic testing.
- Progression to CRPC within 6 months or less of initiation of hormonal therapy.
- Poorly differentiated or transdifferentiated carcinoma.
- PSMA negative/FDG avid disease on PET scan.
- Recovery of adverse events (AEs), including immune-related adverse events (irAEs), to baseline or ≤ Grade 1 severity (CTCAE v5) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable...
- Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
- Platelets (Plt) ≥ 100,000/mm3 without transfusion within 2 weeks of sample collection
- Absolute Neutrophil Count (ANC) ≥ 1500/mm3 without granulocyte colony-stimulating factor support within 2 weeks of sample collection
- Hemoglobin (Hgb) ≥ 9 g/dL without transfusion within 2 weeks of sample collection.
- Calculated creatinine clearance1 ≥ 40 mL/min
- Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine
- Total bilirubin ≤1.5 × upper limit of normal (ULN); ≤ 3 × ULN for people with Gilbert's disease
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Alkaline phosphatase (ALP) ≤ 3 × ULN; ≤ 5 × ULN for people with documented bone metastasis; ≤ 10 x ULN for people with CRPC and bone metastasis if predominantly bone-specific ALP
- International Normalized Ratio (INR) ≤ 1.5 × ULN
- Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 × ULN
- Sexually active fertile people and their partners must agree to use highly effective methods of contraception during the course of the study and for 96 days after the last dose of study drug.
- Projected life expectancy of at least 6 months as determined by treating investigator.
- Ability of the subject to understand and comply with study procedures for the entire length of the study as determined by the enrolling physician or protocol designee.
What rules you out
- Pure small cell carcinoma of the prostate.
- Prior treatment with zanzalintinib.
- Imminent or established spinal cord compression based on clinical and/or imaging findings.
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study drug.
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of start of investigational agent and during the study. Concomitant use of megestrol acetate or...
- Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study drug. Systemic treatment with radionuclides within 6 weeks before first dose of study drug...
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study drug. Note: Eligible...
- Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). Note: people must discontinue prohibited oral anticoagulants within 3 days or 5...
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in people without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week...
- Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study drug.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Unstable deteriorating cardiovascular disorders: i. Congestive heart failure New York...
- Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study drug.
- Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed)
- Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: people with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava)...
- Other clinically significant disorders that would preclude safe study participation. a Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are...
- Major surgery (as defined in Section 5.2.5; eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks...
- Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms per electrocardiogram (ECG) performed within 14 days before first dose of study treatment. Note: Triplicate ECG evaluations will be performed...
- History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
- Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Prior malignancy which required active therapy within 2 years before first dose of study drug. Notes:
- Inclusion of patients with prior malignancies is allowed if the risk of the prior malignancy interfering with either safety or how well it works end points is very low, as assessed by the treating investigator.
- Patients with a previously treated malignancy are eligible to participate if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease.
- Patients who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are allowed to participate.
- Other conditions which, in the opinion of the treating Investigator, would compromise the safety of the patient or the patient's ability to complete the study.
The study team makes the final eligibility decision.
Where it's taking place
- Milwaukee, Wisconsin, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling male, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Milwaukee, Wisconsin, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.