PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors

Breast Neoplasms Clinical Trial

Official title:

A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284723
• Other study ID #: C0541001
• Secondary ID: 2017-002538-22
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2017
• Est. completion date: August 31, 2021

Study information

• Verified date: March 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only)
• HER2 positive and negative breast cancer (Part 2A)
• HER2 negative breast cancer (Part 1B & Part 2B)
• Performance status of 0 or 1
• Adequate bone marrow, kidney and liver function

Exclusion Criteria:

• Known CNS disease including, but not limited to, metastases
• History of exposure to certain cumulative doses of anthracyclines
• Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy
• Active and clinically significant bacterial, fungal, or viral infection
• Abnormal cardiac function defined by a LVEF <50% by ECHO or MUGA
• Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• PF-06804103
Dose Escalation Part - 1A Dose Expansion Part - 2A
• PF-06804103 + Palbociclib +Letrozole
Dose Escalation - Part 1B Dose Expansion - Part 2B

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Macquarie University	Macquarie University	New South Wales
Italy	Divisione di Cardiologia - Istituto Europeo di Oncologia Divisione di Medicina Nucleare	Milano	MI
Italy	Fondazione IRCCS, Istituto Nazionale dei Tumori	Milano	MI
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Azienda Socio-Sanitaria Territoriale Monza	Monza	MB
Italy	Istituto Clinico Humanitas U. O. Oculistica	Razzano	Milan
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Russian Federation	LLC "Clinica UZI 4D"	Pyatigorsk	Stavropol Region
Russian Federation	Private Healthcare Institution "Clinical hospital "RZD-Medicine" of Saint-Petersburg	Saint-Petersburg
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Quirón Madrid	Pozuelo de Alarcón	Madrid
United States	Northside Hospital Inc.- GCS/Athens	Athens	Georgia
United States	Atlanta Cancer Care - Atlanta	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Northside Hospital, Inc. - GCS/Northside	Atlanta	Georgia
United States	Northside Hospital,Inc.-GCS /Blairsville	Blairsville	Georgia
United States	Northside Hospital, Inc. - GCS/Canton	Canton	Georgia
United States	Atlanta Cancer Care - Cumming	Cumming	Georgia
United States	Northside Hospital, Inc.-GCS/Stemmer	Decatur	Georgia
United States	Suburban Hematology-Oncology Associates - Duluth	Duluth	Georgia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Atlanta Cancer Care - Lake Spivey	Jonesboro	Georgia
United States	Suburban Hematology-Oncology Associates- Lawrenceville	Lawrenceville	Georgia
United States	Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	UCLA Health (main campus)	Los Angeles	California
United States	UCLA Hematology/Oncology	Los Angeles	California
United States	Northside Hospital, Inc. - GCS/Macon	Macon	Georgia
United States	Northside Hospital, Inc. GCS/Kennestone	Marietta	Georgia
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	University of Utah, Huntsman Cancer Hospital	Salt Lake City	Utah
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah
United States	Santa Monica - UCLA Medical Center and Orthopaedic Hospital	Santa Monica	California
United States	UCLA Dept of Medicine - Hematology/Oncology, Santa Monica	Santa Monica	California
United States	UCLA Health, Santa Monica	Santa Monica	California
United States	Banner-University Medical Center Tucson	Tucson	Arizona
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	The University of Arizona Cancer Center - North Campus	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Korea, Republic of,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Dose-Limiting Toxicities (DLTs)	First cycle DLTs in order to determine the maximum tolerated dose of monotherapy.	Part 1A: Baseline through Day 21; Part 1B: Baseline through Day 28
Primary	Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Assessment of all available safety data in order to determine the safety and tolerability of monotherapy and combination therapy	Part 1 and Part 2: Baseline through LSLV (up to approximately 2 years)
Primary	Number of participant with objective response	To investigate preliminary antitumor activity	Part 2: Baseline through LSLV (up to approximately 2 years)
Primary	Duration of Response (DR)	To investigate preliminary antitumor activity	Part 2: Baseline through LSLV (up to approximately 2 years)
Primary	Progression-Free Survival (PFS)	To investigate preliminary antitumor activity	Part 2: Baseline through LSLV (up to approximately 2 years)
Primary	Time to Tumor Progression (TTP)	To investigate preliminary antitumor activity	Part 2: Baseline through LSLV (up to approximately 2 years)
Secondary	Maximum Observed Concentration (Cmax) - Part 1A	To understand single and multiple dose parameters	Cycle 1 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycle 2 Day 1 0 and 1 hour, Cycle 3 Day 1 0 and 1 hour, Cycle 4 Day 1 0, 1, 4 and 24 hour, Day 4, Day 8, Day 15, and Day 1 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Maximum Observed Concentration (Cmax) - Part 2A	To understand single and multiple dose parameters	Cycles 1 & 4 on Day 1 at 0, 1, 4 hours, and on Day 15; Cycles 2 & 3 on Day 1 at 0 & 1 hour; Every subsequent cycle pn Day 1 at 0 and 1 hour (cycle is 21 days) up to 24 months
Secondary	Maximum Observed Concentration (Cmax) Part B	To understand single and multiple dose parameters	Cycles 1 & 4 on Day 1 at 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15 at 0 & 1 hour; Cycles 2 & 3 on Day 1 at 0 & 1 hour, Cycles 2 & 3 on Day 15 at 0 & 1 hour; Every subsequent cycle on Day 1 at 0 & 1 hour (cycle is 28 days) up to 24 months
Secondary	Time to reach maximum observed concentration (Tmax) - Part 1A	To understand single and multiple dose parameters	Cycles 1 & 4 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycles 2 & 3 Day 1: 0 and 1 hour, and Day 1: 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Time to reach maximum observed concentration (Tmax) - Part 2A	To understand single and multiple dose parameters	Cycles 1 & 4 on Day 1 at 0, 1, 4 hours, and on Day 15; Cycles 2 & 3 on Day 1 at 0 & 1 hour; Every subsequent cycle pn Day 1 at 0 and 1 hour (cycle is 21 days) up to 24 months
Secondary	Time to reach maximum observed concentration (Tmax) - Part B	To understand single and multiple dose parameters	Cycles 1 & 4 Day 1: 0, 1, 4, and 24 hours, Day 4, Day 8 and Day 15, Cycles 2 & 3 Day 1: 0 and 1 hour, and Day 1: 0 and 1 hour of subsequent cycles (cycle is 28 days) up to 24 months
Secondary	Area under the curve from time zero to end of dosing interval (AUCtau) Part 1A	To understand single and multiple dose parameters	Cycle 1 Day 1 0, 1 4, and 24 hours, Day 4, Day 8 and Day 15, Cycle 2 Day 1 0 and 1 hour, Cycle 3 Day 1 0 and 1 hour, Cycle 4 Day 1 0, 1, 4 and 24 hour, Day 4, Day 8, Day 15, and Day 1 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Area under the curve from time zero to end of dosing interval (AUCtau) Part 2A	To understand single and multiple dose parameters	Cycles 1 and 4: Day 1: 0, 1, 4 hours, and Day 15; Cycle 2 and 3, Day 1: 0 and 1 hour, and Day 1 at 0 and 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Area under the curve from time zero to end of dosing interval (AUCtau) Part B	To understand single and multiple dose parameters	Cycles 1 and 4: Day 1: 0, 1, 4 hours, Day 2, Day 4, Day 8 and Day 15 at 0 and 1 hour; Cycle 2 and 3, Day 1: 0 and 1 hour and Day 15 at 0 and 1 hour, and Day 1 at 0 and 1 hour of subsequent cycles (cycle is 28 days) up to 24 months
Secondary	Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 1A	To understand single and multiple dose parameters	Cycle 1 & Cycle 4 Day 1: 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 2A	To understand single and multiple dose parameters	Cycle 1 & Cycle 4 Day 1: 0, 1, 4 hours, & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 21 days) up to 24 months
Secondary	Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part B	To understand single and multiple dose parameters	Cycle 1 & Cycle 4 Day 1: 0, 1, 4, & 24 hours, Day 4, Day 8 & Day 15, Cycles 2 & 3 Day 1: 0 & 1 hour, and Day 1 at 0 & 1 hour of subsequent cycles (cycle is 28 days) up to 24 months
Secondary	Incidence and titers of anti-drug antibodies Part A	To evaluate the immunogenicity of the drug	Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsequent cycle (each cycle is 21 days) up to 24 months
Secondary	Incidence and titers of anti-drug antibodies Part B	To evaluate the immunogenicity of the drug	Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 28 days) up to 24 months
Secondary	Incidence and titers of neutralizing antibodies Part A	To evaluate the immunogenicity of the drug	Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 21 days) up to 24 months
Secondary	Incidence and titers of neutralizing antibodies Part B	To evaluate the immunogenicity of the drug	Cycle 1 Day 1, Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Day 1 of every subsquent cycle (each cycle is 28 days) up to 24 months
Secondary	Number of participant with objective response	Document antitumor activity	Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months
Secondary	Progression-Free Survival (PFS)	Document antitumor activity	Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months
Secondary	HER2 expression level in patients with documented anti-tumor activity	Explore preliminary antitumor activity	Baseline and Cycle 3 Day 1 (for monotherapy: each cycle is 21 days; for combination therapy: each cycle is 28 days)
Secondary	Duration of Response (DR)	Document antitumor activity	Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months
Secondary	Time to Tumor Progression (TTP)	Document antitumor activity	Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months

External Links

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