PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors

Stopped early · Phase 1

Conditions studied: Breast Neoplasms, Prostate Neoplasms, Neoplasms, Squamous Cell, Melanoma, Mesothelioma, Pancreatic Neoplasms, Colorectal Neoplasms, Carcinoma, Renal Cell, Liver Neoplasms

In brief

A Phase 1 dose escalation and expansion study evaluating safety, tolerability and pharmacokinetics of PF-06952229 in adult patients with advanced solid tumors.

Key facts

Study ID

NCT03685591

Run by

Pfizer

People needed

49

Starts

2018-10-04

Expected to finish

2022-03-30

Last updated by the study team

2024-06-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• For Part 1A: Histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients are intolerant to standard treatment, resistant to standard therapy or for which no standard therapy is available for the following tumor types:
• Breast cancer; Prostate cancer (mCRPC testosterone less than 50 ng/dL); Squamous cell cancer of the head and neck; Melanoma; Mesothelioma; Pancreatic cancer; Colorectal cancer; Renal cell carcinoma; Hepatocellular cancer.
• For Part 1B:
• histological or cytological diagnosis of mCRPC 3 Part 2A and Part 2B:
• Histologically or cytologically confirmed prostate adenocarcinoma metastatic disease.
• Effective castration with serum testosterone levels 0.5 ng/mL (1.7 nmol/L).
• Having received 3 or more cycles of prior docetaxel therapy (before or after abiraterone).
• Having PD while receiving abiraterone acetate within 12 months of abiraterone treatment initiation.
• Progressive disease (PD) by:
• Progression in measurable disease per RECIST 1.1 criteria. Patient with measurable disease must have at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) (CT scan thickness no greater than 5 mm) or magnetic resonance imaging (MRI). Lymph nodes should be greater than or equal to 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion, and bone lesions will be considered non-measurable disease, or
• Appearance of 2 or more new bone lesions (PCWG2). They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results, or
• Rising PSA defined (PCWG2) as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1) taken at least 1 week apart. • Prior abiraterone acetate must be stopped at least 2 weeks before study treatment.
• Patients must have recently obtained archival tumor tissue available for submission to the sponsor (except for Part 2A - monotherapy dose expansion). Patients enrolled in Part 1 and Part 2 should have access to their archival formalin-fixed paraffin-embedded material, collected within 6 months of screening, containing tumor that is of diagnostic quality and representative of their diagnosed malignancy or whenever possible, consent to undergo a biopsy during screening. The sponsor should be contacted if obtaining a new biopsy is not medically feasible for approval to enroll, prior to initiating screening activities.
• Patients entering the study in the subgroup(s) requiring mandatory pre- and on treatment tumor biopsies in Part 2A and 2B must have a tumor amenable to biopsy and consent to these planned biopsy procedures. The sponsor should be contacted if obtaining a pre-treatment and on treatment biopsies is not medically feasible for approval to enroll, prior to initiating screening activities.
• Age 18 years or older 7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 8. Adequate bone marrow function (see Appendix 3), including:
• Absolute Neutrophil Count (ANC) greater than or equal to 1,500/mm3;
• Platelets greater than or equal to 100,000/mm3;
• Hemoglobin greater than or equal to 9 g/dL. 9. Adequate renal function, including serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or estimated creatinine clearance greater than or equal to 60 mL/min as calculated using the method standard for the institution. In equivocal cases, a 24 hour urine collection test can be used to estimate the creatinine clearance more accurately. In Part 2: Serum creatinine of less than or equal to 3.0 x upper limit of normal.
• Adequate liver function, including:
• Total serum bilirubin less than or equal to 0.5 x ULN unless the patient has documented Gilbert syndrome;
• Aspartate and alanine aminotransferase (AST and ALT) less than or equal to 2.5 x ULN less than or equal to 5.0 x ULN if there is liver involvement by the tumor;
• Alkaline phosphatase less than or equal 2.5 x ULN less than or equal to 5 x ULN in case of bone metastasis).
• Serum phosphate within normal range (if abnormal, must be nonclinically significant per the Investigator and approval for patient inclusion after agreement from sponsor.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for alopecia and those listed in the specific exclusion criteria.
• For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening.

You may not qualify if…

• Patients with any of the characteristics/conditions listed below will not be included in the study:
• Any labs may be repeated for confirmation. Only the lab result requiring confirmation must be repeated, not the entire panel.
• For Parts 1B current or prior treatment with enzalutamide within 24 days prior to first dose
• For 2A, and 2B:
• Prior chemotherapy other than docetaxel for prostate cancer, except estramustine, adjuvant/neoadjuvant treatment completed more than 3 years ago;
• Less than 28 days elapsed from prior treatment with chemotherapy, immunotherapy, radiotherapy, or surgery to the time of study enrollment.
• Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by baseline brain MRI (or CT with contrast if MRI is medically contraindicated), clinical symptoms, cerebral edema, and/or progressive growth. If contrast is medically contraindicated, a non-contrast CT scan may be performed.
• Patients with a history of CNS metastases or cord compression.
• Liver metastases at baseline as evidenced by CT scan or MRI that may be at risk for bleeding, such as those that are greater than 1 cm,
• Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement). Note: Patients with indwelling catheter for drainage, or requirement for drainage no more frequently than monthly will be allowed.
• Any other active malignancy within 3 years prior to study entry, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Patients with a history of clinically significant tumor bleeding (except for bleeding in a post-operative setting), coagulopathy or arterio-venous malformations (AVM) or aneurysms in the CNS, liver, lung or other major organ of the body. Patients with known Osler-Weber-Rendu disease, Hemophilia A, Hemophilia B (Christmas Disease), Von Willibrand's Disease, Factor 13 deficiency and Factor 7 deficiency, antibodies to Factors 8 and 7, history of other bleeding diatheses and abnormal INR values.
• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the investigator is likely to bleed.
• Major surgery within 4 weeks prior to first dose.
• Prior organ transplantation including heart and allogeneic stem cell transplantation.
• Radiation therapy within 4 weeks prior to study entry. Note: Patients who have received radiotherapy must have recovered from any reversible side effects, such as nausea and vomiting.
• Last anti cancer therapy including investigational drug(s) within 28 days (or 5 half-lives, whichever is shorter) prior to study entry excluding hormonal therapy.
• Active and clinically significant bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), known hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. In equivocal cases, with positive serology, those patients with a negative viral load are potentially eligible provided the other entry criteria are met. Note: Inclusion of patients with well controlled HIV, HBV or HCV can be discussed with sponsor on a case by case basis.
• COVID-19/SARS-CoV2: Refer to Appendix 8 for further information.
• Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep venous thrombosis (DVT); arterial occlusive disease; ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE Grade 2 or higher , atrial fibrillation of any grade that is uncontrolled, or QTcF interval greater than 470 msec at screening. Note: There is an exception where a cardiac rhythm device/pacemaker is fitted and results in QTcF greater than 470 msec.
• Anticoagulation therapy with heparin, low molecular weight heparin, vitamin K antagonists, anti-platelet agents, or factor Xa inhibitors throughout the study and for at least 28 days post the last dose of study treatment. (If anticoagulation therapy is medically indicated on trial, patients should stop treatment with PF-06952229. For those requiring temporary anticoagulant therapy, resumption of PF-06952229 treatment may be permitted after discussion with the Sponsor. In any other case, study treatment should be permanently discontinued, and the patient should enter the follow-up portion of the trial.)
• Moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation.
• Evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels.
• Grade 3 or higher cardiac troponin I at baseline.
• Left ventricular ejection fraction (LVEF) of less than or equal to 50% or significant valvular regurgitation.

Where it is running

• HonorHealth — Scottsdale, Arizona, United States
• UCLA Dept of Medicine -Hematology/Oncology,Santa Monica — Santa Monica, California, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Mass General/ North Shore Center for Outpatient Care — Danvers, Massachusetts, United States
• Dana-Farber Cancer Institute - Chestnut Hill — Newton, Massachusetts, United States
• OU Medical Center Presbyterian Tower — Oklahoma City, Oklahoma, United States
• Stephenson Cancer Center — Oklahoma City, Oklahoma, United States
• Sarah Cannon Research Institute - Pharmacy — Nashville, Tennessee, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• The Sarah Cannon Research Institute / Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• The Sarah Cannon Research Institute — Nashville, Tennessee, United States
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• NEXT Oncology — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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