PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03460977

Collaborator

(none)

185

Enrollment

Locations

Arms

87.1

Anticipated Duration (Months)

3.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer (SCLC) Follicular Lymphoma (FL) Castration Resistant Prostate Cancer (CRPC)	Drug: PF-06821497	Phase 1

Detailed Description

This is an open label, multi center, Phase 1 dose escalation and dose expansion study of PF-06821497 administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. Part 1A will evaluate safety and target modulation of PF-06821497 monotherapy in patients with SCLC, FL and CRPC. PF-06821497 will be administered as monotherapy in patients with FL in Part 1B dose escalation and to patients with CRPC in Part 1C dose escalation. For Part 2A (dose escalation combination therapy), PF-06821497 will be administered in combination with SOC in patients with CRPC and SCLC. For Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or PF-06821497 in combination with SOC. Once safety and adequate target modulation has been established in Part 1A, Parts 1B and 2A of the trial will be initiated. Part 1C (monotherapy dose escalation) will determine the MTD of single agent PF-06821497 in patients with mCRPC. Part 2A (escalation RP2D finding for combination) will determine the MTD of the combination with SOC in patients with CRPC. Part 2B (dose expansion) will assess the efficacy of PF-06821497 at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

185 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Apr 17, 2018

Anticipated Primary Completion Date :

Jul 20, 2025

Anticipated Study Completion Date :

Jul 20, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation (Part 1A) Participants with SCLC, CRPC and FL will receive PF-06821497 at escalating dose levels	Drug: PF-06821497 Oral continuous
Experimental: Dose Escalation (Part 1B) Participants with FL will receive PF-06821497 at escalating dose levels	Drug: PF-06821497 Oral continuous
Experimental: Dose Escalation (Part 1C) Participants with CRPC will receive PF-06821497 at escalating dose levels.	Drug: PF-06821497 Oral continuous
Experimental: Dose Escalation (Part 2A) Participants with CRPC and SCLC will receive PF-06821497 at escalating dose levels in combination with SOC.	Drug: PF-06821497 Oral continuous
Experimental: Dose Expansion (Part 2B) Participants with CRPC will receive PF-06821497 in combination with SOC or SOC alone.	Drug: PF-06821497 Oral continuous

Outcome Measures

Primary Outcome Measures

Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) [Baseline up to 90 days]
First cycle DLTs will be utilized to determine the MTD
Overall safety profile including adverse events [Baseline up to approximately 2 years]
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03])
Preliminary efficacy determination as evaluated by disease specific response criteria [Through study completion, approximately 2 years past last patient first visit.]
Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC.
Overall safety profile including laboratory abnormalities [Baseline up to approximately 2 years]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.
Overall safety profile including vital signs [Baseline up to approximately 2 years]
Vital sign changes from baseline including blood pressure, heart rate, ECG changes.

Secondary Outcome Measures

Evaluate time to event anti-tumor activity of PF-06821497 including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type. [Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.]
Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Working Group 3 (PWG3) for Castration Resistant Prostate Cancer (CRPC)
Evaluate overall survival [Baseline up to approximately 2 years]
Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) [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]
Single dose and multiple dose PK will be calculated as data permits including Maximum Observed Plasma Concentration (Cmax).
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax) [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]
Single dose and multiple dose PK will be calculated as data permits including Time to Reach Maximum Observed Plasma Concentration (Tmax).
Pharmacokinetic Parameters: Area Under the Curve (AUC) [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]
Single dose and multiple dose PK will be calculated as data permits including Area Under the Cuvce (AUC).
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F) [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]
Single dose and multiple dose PK will be calculated as data permits including Apparent Oral Clearance (CL/F). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F) [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]
Single dose and multiple dose PK will be calculated as data permits including Apparent Volume of Distribution (Vz/F). Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2) [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]
Singe dose and multiple dose PK will be calculated as data permits including Plasma Decay Half-Life (t1/2). Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Evaluate the impact of PF-06821497 on patient reported outcomes. [Cycle 1 Day 1, Cycle 2 Day 1, Cycle 6 Day 1, Cycle 10 Day 1, Cycle 14 Day 1, Cycle 18 Day 1, Cycle 22 Day 1, Cycle 26 Day 1, Cycle 30 Day 1 and at End of Treatment visit.]
Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:

Part 1A (closed to enrollment):

Advanced/unresectable or metastatic SCLC, CRPC 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 (closed to enrollment):

FL; patients should have exhausted all curative therapies and have relapsed or refractory disease.

Part 1C:

Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PWG3)

Part 2A:

Treatment naïve extensive disease SCLC patients;
Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PWG3)

Part 2B:

Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, and have evidence of prostate cancer progression (per PWG3) Patients must have radiographic evidence of disease

Other inclusion criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Adequate organ function

Key Exclusion Criteria:

Prior Chemotherapy: Part 1C (CRPC): no more than 2 previous regimens of chemotherapy

Part 2A:

CRPC: no more than 1 previous regimen of systemic chemotherapy SCLC: must be chemotherapy naive for SCLC (may have received one cycle of chemotherapy after discussion with the sponsor) Part 2B (CRPC): no more than 1 previous regimen of chemotherapy i

Prior irradiation to >25% of the bone marrow.
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.
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 inducers or 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urological Associates of Southern Arizona, P.C .	Tucson	Arizona	United States	85715
2	Banner-University Medical Center Tucson	Tucson	Arizona	United States	85719
3	The University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	The University of Arizona Cancer Center	Tucson	Arizona	United States	85724-5024
5	Urological Associates of Southern Arizona, PC	Tucson	Arizona	United States	85741
6	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California	United States	91010
7	City of Hope Investigational Drug Services (IDS)	Duarte	California	United States	91010
8	Norwalk Hospital	Norwalk	Connecticut	United States	06856
9	Illinois CancerCare, P.C.	Peoria	Illinois	United States	61615
10	The University of Kansas Cancer Center, Investigational Drug Services	Fairway	Kansas	United States	66205
11	The University of Kansas Clinical Research Center	Fairway	Kansas	United States	66205
12	The University of Kansas Hospital	Kansas City	Kansas	United States	66160
13	The University of Kansas Medical Center Medical Office Building	Kansas City	Kansas	United States	66160
14	The University of Kansas Cancer Center - Indian Creek Campus	Overland Park	Kansas	United States	66211
15	The University of Kansas Cancer Center	Westwood	Kansas	United States	66205
16	Norton Cancer Institute Pharmacy, Downtown Pharmacy	Louisville	Kentucky	United States	40202
17	Norton Cancer Institute Pharmacy	Louisville	Kentucky	United States	40202
18	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky	United States	40202
19	Norton Hospital	Louisville	Kentucky	United States	40202
20	Maryland Oncology Hematology, P.A.	Rockville	Maryland	United States	20850
21	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
22	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
23	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
24	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
25	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
26	OU Medical Center Presbyterian Tower	Oklahoma City	Oklahoma	United States	73104
27	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
28	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
29	Parkway Surgery Center	Myrtle Beach	South Carolina	United States	29572
30	Tennessee Oncolgy, PLLC	Nashville	Tennessee	United States	37203
31	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
32	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
33	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
34	Texas Oncology -Fort Worth Cancer Center	Fort Worth	Texas	United States	76104
35	US Oncology Investigational Product Center (IPC)	Irving	Texas	United States	75063
36	US Oncology Investigational Product Center (IPC)	Irving	Texas	United States	75063
37	US Oncology Investigational Products Center	Irving	Texas	United States	75063
38	NEXT Oncology	San Antonio	Texas	United States	78240
39	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
40	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
41	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
42	LLC "Neyro-klinika"	Moscow		Russian Federation	117186
43	Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department	Moscow		Russian Federation	125284
44	SBHI of Moscow City Clinical Hospital	Moscow		Russian Federation	129301
45	Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"	Omsk		Russian Federation	644013
46	Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov	Saint Petersburg		Russian Federation	197341
47	Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"	Saint Petersburg		Russian Federation	198255
48	Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨	Saint-Petersburg		Russian Federation	195271
49	Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N.	Saint-Petersburg		Russian Federation	197758
50	State Budgetary Healthcare Institution of the Yaroslavl Region	Yaroslavl		Russian Federation	150054
51	Institut Català d´Oncología (ICO)-H. Durán i Reynals	L'Hospitalet de Llobregat	Barecelona	Spain	08908
52	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
53	Hospital Clinic de Barcelona	Barcelona		Spain	08036
54	Consorcio Hospitalario Provincial de Castellon	Castellon		Spain	12002
55	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
56	H.U. Fundación Jiménez Díaz	Madrid		Spain	28040
57	Hospital Universitario 12 De Octubre	Madrid		Spain	28041
58	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050