PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors

NCT03685591 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: C3881001
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 15

Brief Summary

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

Conditions

Breast Neoplasms; Prostate Neoplasms; Neoplasms, Squamous Cell; Melanoma; Mesothelioma; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Renal Cell; Liver Neoplasms

Keywords

efficacy; safety; pharmacokinetics; dose escalation; dose expansion; open-label; TGFb; transforming growth factor beta; breast cancer; prostate cancer; CRPC; metastatic; advanced; adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

• 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.

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

• 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.

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

Secondary Outcomes (16)

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

  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.

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

  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.

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

  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.

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

  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.

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

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

Study Arms (15)

Dose Level 1 (Part 1A)

EXPERIMENTAL

PF-06952229 at 20mg twice daily (BID)

Drug: PF-06952229

Dose Level 2 (Part 1A)

EXPERIMENTAL

PF-06952229 at 40 mg BID

Drug: PF-06952229

Dose Level 3 (Part 1A)

EXPERIMENTAL

PF-06952229 at 80 mg BID

Drug: PF-06952229

Dose Level 4 (Part 1A)

EXPERIMENTAL

PF-06952229 at 150 mg BID

Drug: PF-06952229

Dose Level 5 (Part 1A)

EXPERIMENTAL

PF-06952229 at 250 mg BID

Drug: PF-06952229

Dose Level 6 (Part 1A)

EXPERIMENTAL

PF-06952229 at 375 mg BID

Drug: PF-06952229

Dose Level 7 (Part 1A)

EXPERIMENTAL

PF-06952229 at 500 mg BID

Drug: PF-06952229

Dose Level 8 (Part 1A)

EXPERIMENTAL

PF-06952229 at 625 mg BID

Drug: PF-06952229

Dose Level 9 (Part 1A)

EXPERIMENTAL

PF-06952229 at 750 mg BID

Drug: PF-06952229

Prostate Cancer Dose Level 1 (Part 1B)

EXPERIMENTAL

PF-06952229 at 375 mg BID in combination with enzalutamide

Drug: PF-06952229; Drug: Enzalutamide

Prostate Cancer Dose Level 2 (Part 1B)

EXPERIMENTAL

PF-06952229 at 500 mg BID in combination with enzalutamide

Drug: PF-06952229; Drug: Enzalutamide

Prostate Cancer Dose Level 3 (Part 1B)

EXPERIMENTAL

PF-06952229 at 625 mg BID in combination with enzalutamide

Drug: PF-06952229; Drug: Enzalutamide

Prostate Cancer Dose Level 4 (Part 1B)

EXPERIMENTAL

PF-06952229 at 750 mg BID in combination with enzalutamide

Drug: PF-06952229; Drug: Enzalutamide

Prostate Cancer (Part 2A)

EXPERIMENTAL

PF-06952229 at recommended Phase 2 Dose BID

Drug: PF-06952229

Prostate Cancer (Part 2B)

EXPERIMENTAL

PF-06952229 at recommended phase 2 dose BID in combination with enzalutamide

Drug: PF-06952229; Drug: Enzalutamide

Interventions

PF-06952229 DRUG

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

Dose Level 1 (Part 1A); Dose Level 2 (Part 1A); Dose Level 3 (Part 1A); Dose Level 4 (Part 1A); Dose Level 5 (Part 1A); Dose Level 6 (Part 1A); Dose Level 7 (Part 1A); Dose Level 8 (Part 1A); Dose Level 9 (Part 1A); Prostate Cancer (Part 2A); Prostate Cancer (Part 2B); Prostate Cancer Dose Level 1 (Part 1B); Prostate Cancer Dose Level 2 (Part 1B); Prostate Cancer Dose Level 3 (Part 1B); Prostate Cancer Dose Level 4 (Part 1B)

Enzalutamide DRUG

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

Prostate Cancer (Part 2B); Prostate Cancer Dose Level 1 (Part 1B); Prostate Cancer Dose Level 2 (Part 1B); Prostate Cancer Dose Level 3 (Part 1B); Prostate Cancer Dose Level 4 (Part 1B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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:

You may not qualify if:

• \. For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening.
• \. 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.
• \. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
• \. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (15)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

UCLA Dept of Medicine -Hematology/Oncology,Santa Monica

Santa Monica, California, 90404, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mass General/ North Shore Center for Outpatient Care

Danvers, Massachusetts, 01923, United States

Location

Dana-Farber Cancer Institute - Chestnut Hill

Newton, Massachusetts, 02459, United States

Location

OU Medical Center Presbyterian Tower

Oklahoma City, Oklahoma, 73104, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute / Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 39214047 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms; Neoplasms, Squamous Cell; Melanoma; Mesothelioma; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Renal Cell; Liver Neoplasms; Camurati-Engelmann Syndrome; Neoplasm Metastasis; Adenocarcinoma

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Adenoma; Neoplasms, Mesothelial; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Kidney Neoplasms; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases; Liver Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial began on 04 October 2018 with LPLV occurring on 30 March 2022 following Pfizer's strategic decision (not due to any specific safety reasons or request from a regulatory authority) to terminate the study, which included the period during which the COVID-19 pandemic was occurring globally since 11 March 2020.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 26, 2018
• Study Start: October 4, 2018
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)