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Breast NeoplasmsPhase 1NCT03685591

PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors

A Phase 1 study testing PF-06952229 and Enzalutamide in people with Breast Neoplasms and Prostate Neoplasms, run by Pfizer at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
PF-06952229 and Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
15 sitesUnited States
Study dates
4 Oct 2018to 30 Mar 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 10. 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).
  • 11. Serum phosphate within normal range (if abnormal, must be nonclinically significant per the Investigator and approval for patient inclusion after agreement from sponsor.
  • 12. 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.
  • 13. For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening.
  • 14. For Part 1A monotherapy dose escalation: female patients of nonchildbearing potential must meet at least 1 of the following criteria:
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and must have a serum follicle stimulating hormone level confirming the postmenopausal state;
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
  • 15. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
  • 16. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Who cannot join

  • 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.
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  • 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.
  • Hypertension that cannot be controlled by medications (greater than 150/90 mmHg despite optimal medical therapy) or requiring more than 2 medications for adequate control.
  • Clinically significant non healing or healing wounds.
  • For patients entering the combination with enzalutamide arm, history of seizures other than isolated febrile seizure in childhood.
  • Has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
  • Known or suspected hypersensitivity to active ingredient/excipients of PF 06952229 or enzalutamide.
  • Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
  • For Part 1A Monotherapy Dose Escalation: Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
  • For Part 1B Combination Dose Escalation, Part 2A Monotherapy Expansion, and Part 2B Combination Dose Expansion: fertile male patients and female partners of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose for monotherapy (Part 2A) or for at least 3 months after the last dose for combination therapy (Part 1B and Part 2B).
  • Inability to consume or absorb study drug, including but not limited to:
  • Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery. Impairment of gastro intestinal function or GI disease that may significantly alter the absorption of PF 06952229, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade greater than 1.
  • Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer, prior to first dose of investigational product.
  • Current use or anticipated need for drugs that are known strong and moderate CYP3A4/5 inducers, including their administration within 10 days or 5 half lives of the CYP3A4/5 inducer, whichever is longer, prior to the first dose of investigational product (See Section 5.7).
  • Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa B ligand (RANK L) targeted agents (for example, denosumab) less than 14 days prior to study entry, unless there is agreement with the medical monitor.
  • Active, known suspect suspected autoimmune diseases including inflammatory bowel disease (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus (SLE), autoimmune vasculitis (eg, Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune origin (eg, Gullian Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Mass General/ North Shore Center for Outpatient Care

    Danvers, Massachusetts, 01923

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Sarah Cannon Research Institute - Pharmacy

    Nashville, Tennessee, 37203

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • The Sarah Cannon Research Institute / Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • The Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Dana-Farber Cancer Institute - Chestnut Hill

    Newton, Massachusetts, 02459

  • OU Medical Center Presbyterian Tower

    Oklahoma City, Oklahoma, 73104

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • NEXT Oncology

    San Antonio, Texas, 78229

  • UCLA Dept of Medicine -Hematology/Oncology,Santa Monica

    Santa Monica, California, 90404

  • HonorHealth

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

Official title: A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF 06952229 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS

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

Read the detailed description

This is a Phase 1, open label, multi center, multiple dose, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06952229 in previously treated patients with advanced or metastatic cancers that may have high TGFbeta signatures and EMT expression.

The study includes Parts 1A and 1B, which are dose-escalation for monotherapy and combination therapy with enzalutamide, respectively, and Parts 2A and 2B, which are dose expansion for monotherapy and combination therapy with enzalutamide, respectively.

Being tested
PF-06952229, Enzalutamide
Keywords
efficacy, safety, pharmacokinetics, dose escalation, dose expansion, open-label, TGFb, transforming growth factor beta, breast cancer, prostate cancer, CRPC, metastatic, advanced, adenocarcinoma
Medical subject headings
Breast Neoplasms, Prostatic Neoplasms, Neoplasms, Squamous Cell, Melanoma, Mesothelioma, Pancreatic Neoplasms, Colorectal Neoplasms, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-06952229Drug

    Oral 7 days on / 7 days off - 28 day cycles (Part 1)

  • EnzalutamideDrug

    Prostate Cancer (Part 2). 160mg, capsules, orally, daily

Study groups in NCT03685591
Study groupRoleWhat they receive
Dose Level 1 (Part 1A)ExperimentalPF-06952229 at 20mg twice daily (BID)
Receives: Drug: PF-06952229
Dose Level 2 (Part 1A)ExperimentalPF-06952229 at 40 mg BID
Receives: Drug: PF-06952229
Dose Level 3 (Part 1A)ExperimentalPF-06952229 at 80 mg BID
Receives: Drug: PF-06952229
Dose Level 4 (Part 1A)ExperimentalPF-06952229 at 150 mg BID
Receives: Drug: PF-06952229
Dose Level 5 (Part 1A)ExperimentalPF-06952229 at 250 mg BID
Receives: Drug: PF-06952229
Dose Level 6 (Part 1A)ExperimentalPF-06952229 at 375 mg BID
Receives: Drug: PF-06952229
Dose Level 7 (Part 1A)ExperimentalPF-06952229 at 500 mg BID
Receives: Drug: PF-06952229
Dose Level 8 (Part 1A)ExperimentalPF-06952229 at 625 mg BID
Receives: Drug: PF-06952229
Dose Level 9 (Part 1A)ExperimentalPF-06952229 at 750 mg BID
Receives: Drug: PF-06952229
Prostate Cancer Dose Level 1 (Part 1B)ExperimentalPF-06952229 at 375 mg BID in combination with enzalutamide
Receives: Drug: PF-06952229; Drug: Enzalutamide
Prostate Cancer Dose Level 2 (Part 1B)ExperimentalPF-06952229 at 500 mg BID in combination with enzalutamide
Receives: Drug: PF-06952229; Drug: Enzalutamide
Prostate Cancer Dose Level 3 (Part 1B)ExperimentalPF-06952229 at 625 mg BID in combination with enzalutamide
Receives: Drug: PF-06952229; Drug: Enzalutamide
Prostate Cancer Dose Level 4 (Part 1B)ExperimentalPF-06952229 at 750 mg BID in combination with enzalutamide
Receives: Drug: PF-06952229; Drug: Enzalutamide
Prostate Cancer (Part 2A)ExperimentalPF-06952229 at recommended Phase 2 Dose BID
Receives: Drug: PF-06952229
Prostate Cancer (Part 2B)ExperimentalPF-06952229 at recommended phase 2 dose BID in combination with enzalutamide
Receives: Drug: PF-06952229; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment

    First cycle DLTs were utilized to determine the max tolerated dose and future escalations or deescalations. Any of the following adverse events occurred in the first cycle of treatment which were clinically significant were classified as DLTs: Hematologic: Thrombocytopenia Grade 4 for >=7 days, or Grade 3 or 4 associated with >= Grade 2 clinically significant bleeding or requiring platelet transfusion; Neutropenia Grade 4 for >=7 days; Grade>=3 neutropenia with infection; Anemia Grade 4 or Grade 3 requiring blood transfusion. Nonhematologic: Grade>=3 toxicities that were considered clinically significant; Alanine aminotransferase/aspartate aminotransferase>3x the upper limit of normal (ULN) with bilirubin>2x ULN without another explanation; Grade 3 nausea, vomiting or diarrhea that did not resolve within 4 days despite maximal supportive therapy. Nonhematologic and Non-Hepatic: Any toxicity caused>= 2 weeks of dose delay or preventing participants from receiving 75% of study drug.

    Measured: Within 28 days of first dose or until the participant completed the first cycle of therapy if there were treatment delayed (on average 28 days).

  2. Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.

    Measured: Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years)

  3. Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

    Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters was determined at the investigator's discretion.

    Measured: Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years)

Secondary outcomes (16)

  1. Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A)

    Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  2. Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B)

    Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  3. Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A)

    Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  4. Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B)

    Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  5. Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A)

    AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  6. Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B)

    AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  7. Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A)

    AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  8. Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B)

    AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  9. Apparent Clearance (CL/F) of PF-06952229 (Part 1A)

    Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  10. Apparent Clearance (CL/F) of PF-06952229 (Part 1B)

    Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  11. Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A)

    Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf* kel) for single dose; Vz/F = Dose / (AUCtau* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  12. Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B)

    Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf* kel) for single dose; Vz/F = Dose / (AUCtau* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  13. Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A)

    Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.

  14. Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B)

    Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration.

    Measured: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2

  15. Number of Participants With Prostate Specific Antigen 50 (PSA50) Response

    Prostate-specific antigen decline by more than 50% from baseline was analyzed. PSA partial response was defined as a ≥50% decline in PSA from Cycle 1 Day 1 (baseline) PSA value. This PSA decline much be confirmed to be sustained by a second PSA value obtained 4 or more weeks later.

    Measured: Baseline, Cycle 1 Day 1 (at the beginning of Cycle 1), and then every 3 cycles (each cycle is 28 days) until end of treatment (an average of 1 year)

  16. Percentage of Participants With Objective Response

    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). Complete response was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). All target lesions must be assessed. Partial response was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.

    Measured: Baseline and every 8 to 12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2018
  2. Study start4 Oct 2018
  3. Primary completion30 Mar 2022
  4. Study completion30 Mar 2022

Why it stopped: The decision to stop enrollment was due to strategic considerations and not due to any specific safety reasons or request from a regulatory authority.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03685591
Sponsor's protocol ID
C3881001
Other IDs
C3881001
Status last verified
Jun 2024
First submitted
20 Sep 2018
Last updated
26 Jun 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Yap TA, Choudhury AD, Hamilton E, Rosen LS, Stratton KL, Gordon MS, Schaer D, Liu L, Zhang L, Mittapalli RK, Zhong W, Soman N, Tolcher AW. PF-06952229, a selective TGF-beta-R1 inhibitor: preclinical development and a first-in-human, phase I, dose-escalation study in advanced solid tumors. ESMO Open. 2024 Sep;9(9):103653. doi: 10.1016/j.esmoop.2024.103653. Epub 2024 Aug 29.

    PubMed 39214047

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-06952229 and Enzalutamide in people with Breast Neoplasms and Prostate Neoplasms, run by Pfizer at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment (time frame: Within 28 days of first dose or until the participant completed the first cycle of therapy if there were treatment delayed (on average 28 days).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03685591, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2024.

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