A Phase I Dose Escalation And Expanded Cohort Study Of Pf-06821497 In The Treatment Of Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (Sclc), Castration Resistant Prostate Cancer (Crpc) And Follicular Lymphoma (fl)

Uncategorized

A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF-06821497 IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)

Condition: Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL), Castration Resistant Prostate Cancer (CRPC), Diffuse Large B-Cell Lymphoma (DLBCL)

Intervention:

  • Drug: PF-06821497

Purpose: A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03460977

Sponsor: Pfizer

Primary Outcome Measures:

  • Measure: Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
  • Time Frame: Baseline up to 90 days
  • Safety Issue:
  • Measure: Overall safety profile including adverse events
  • Time Frame: Baseline up to approximately 2 years
  • Safety Issue:
  • Measure: Preliminary efficacy determination as evaluated by disease specific response criteria
  • Time Frame: Through study completion, approximately 2 years past last patient first visit.
  • Safety Issue:
  • Measure: Overall safety profile including laboratory abnormalities
  • Time Frame: Baseline up to approximately 2 years
  • Safety Issue:
  • Measure: Overall safety profile including vital signs
  • Time Frame: Baseline up to approximately 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), and metastatic free survival (MFS)
  • Time Frame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
  • Safety Issue:
  • Measure: Evaluate overall survival
  • Time Frame: Baseline up to approximately 2 years
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Area Under the Curve (AUC)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:
  • Measure: Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
  • Time Frame: Cycle 1, Day 1, pre dose, 0.25, 0.5, 1, 2, 3, 4, 6, and 10 or 12 hours post dose; Cycle 1 Day 8, pre dose; Cycle 1 Day 15 pre dose, 0.25, 0.5, 1, 2, 3, 4, 6 and 10 or 12 hours post dose, Cycle ≥2 Day 1 pre dose; End of Treatment visit
  • Safety Issue:

Estimated Enrollment: 172

Study Start Date: April 19, 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts: Part 1A: -Histologically / cytologically confirmed advanced/unresectable or metastatic SCLC, CRPC, DLBCL and FL that is refractory to or intolerable of standard treatment, or for which no curative treatment is available. Note for FL (Parts 1A and 1B) during the dose finding phase of study, follicular lymphoma patients must have exhausted all standard of care therapies. Part 1B: Histologically confirmed FL patients that have exhausted all curative therapies and have relapsed or refractory disease. Part 2:
  • Histologically or cytologically confirmed treatment naïve extensive disease SCLC patients;
  • Histologically confirmed FL patients that are intolerant of or resistant to standard therapy or for which no curative therapy is available and have relapsed or refractory disease (Part 2B).
  • Histological / cytological diagnosis of castration resistant prostate cancer. Received either abiraterone and/or enzalutamide treatment and has evidence of prostate cancer progression (per PWG3):
  • SCLC patients entering the study in the expansion cohort with at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • FL patients entering the study in the expansion cohort with at least one measurable lesion as defined by Response Evaluation Criteria in Lymphoma (RECIL) criteria.
  • Females and/or male patients age 18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  • Adequate Bone Marrow Function
  • Adequate Renal Function
  • Adequate Liver Function
  • Serum pregnancy test (for females of childbearing potential) negative at screening, and negative serum or urine pregnancy test at baseline prior to treatment administration.

Exclusion Criteria:

  • Known symptomatic brain metastases requiring steroids or CNS involvement in FL. Previously diagnosed brain metastases are eligible if they have been treated and recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Physiologic replacement doses of corticosteroids are permissible.
  • At least 3 weeks since last major surgery (a lesser period is acceptable if decided to be in the best interest of the SCLC patient).
  • Treatment with more than 2gm acetaminophen per day within 14 days of study entry and on study if required.
  • Chronic liver diseases.
  • History of alcohol abuse or binge drinking in the last 6 months prior to screening.
  • 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.
  • Systemic anti cancer therapy
  • approved or investigational
  • within 4 weeks or 5 half-lives, whichever is shorter, prior to study entry, including antibody based agents. Prostate cancer cohorts 2A and 2B must have not received more than 1 previous regimen of systemic chemotherapy in mCPRC setting. SCLC cohorts must be chemotherapy naive for SCLC however may have received one cycle of chemotherapy after discussion with the sponsor.
  • Last anti hormonal therapy within 2 weeks prior to C1D1.
  • Prior stem cell transplant, autologous or allogenic, within 100 days prior to study enrollment or patients who experienced graft veses host disease or who require systemic immune suppressive therapy.
  • Prior irradiation to >25% of the bone marrow.
  • Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
  • 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; ongoing cardiac dysrhythmias of NCI CTCAE Grade 2, atrial fibrillation of any grade, or QTcF interval >480 msec at screening.
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
  • Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC) or platinum compound.
  • 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.
  • 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 28days after the last dose of investigational product.
  • Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
  • Current use or anticipated need for food or drugs that are known strong 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 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.

Contact:

  • Pfizer CT.gov Call Center
  • 1-800-718-1021

Locations:

  • Urological Associates of Southern Arizona, P.C .
  • Tucson Arizona 85715 United States
  • Banner-University Medical Center Tucson
  • Tucson Arizona 85719 United States
  • The University of Arizona Cancer Center-North Campus
  • Tucson Arizona 85719 United States
  • The University of Arizona Cancer Center
  • Tucson Arizona 85724-5024 United States
  • Urological Associates of Southern Arizona, PC
  • Tucson Arizona 85741 United States
  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
  • Duarte California 91010 United States
  • City of Hope Investigational Drug Services (IDS)
  • Duarte California 91010 United States
  • Norwalk Hospital
  • Norwalk Connecticut 06856 United States
  • Norton Cancer Institute, Norton Healthcare Pavilion
  • Louisville Kentucky 40202 United States
  • Norton Hospital
  • Louisville Kentucky 40202 United States
  • Brigham and Women’s Hospital
  • Boston Massachusetts 02115 United States
  • Dana Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Hackensack University Medical Center
  • Hackensack New Jersey 07601 United States
  • John Theurer Cancer Center at Hackensack University Medical Center
  • Hackensack New Jersey 07601 United States
  • OU Medical Center Presbyterian Tower
  • Oklahoma City Oklahoma 73104 United States
  • Stephenson Cancer Center
  • Oklahoma City Oklahoma 73104 United States
  • Tennessee Oncolgy, PLLC
  • Nashville Tennessee 37203 United States
  • Tennessee Oncology, PLLC
  • Nashville Tennessee 37203 United States
  • The Sarah Cannon Research Institute
  • Nashville Tennessee 37203 United States
  • The University of Texas MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • NEXT Oncology
  • San Antonio Texas 78240 United States
  • Virginia Cancer Specialists, PC
  • Fairfax Virginia 22031 United States
  • Seattle Cancer Care Alliance
  • Seattle Washington 98109 United States

View trial on ClinicalTrials.gov

X