Clinical Trials /

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

NCT03284723

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors
  • 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 IDs

  • ORG STUDY ID: C0541001
  • SECONDARY ID: 2017-002538-22
  • NCT ID: NCT03284723

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
PF-06804103PF-06804103
PF-06804103 + Palbociclib +LetrozolePF-06804103+Combination Regimen

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PF-06804103ExperimentalStudy Treatment
  • PF-06804103
PF-06804103+Combination RegimenExperimentalStudy Treatment
  • PF-06804103 + Palbociclib +Letrozole

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose-Limiting Toxicities (DLTs)
Time Frame:Part 1A: Baseline through Day 21; Part 1B: Baseline through Day 28
Safety Issue:
Description:First cycle DLTs in order to determine the maximum tolerated dose of monotherapy.

Secondary Outcome Measures

Measure:Maximum Observed Concentration (Cmax) - Part 1A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Maximum Observed Concentration (Cmax) - Part 2A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Maximum Observed Concentration (Cmax) Part B
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Time to reach maximum observed concentration (Tmax) - Part 1A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Time to reach maximum observed concentration (Tmax) - Part 2A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Time to reach maximum observed concentration (Tmax) - Part B
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the curve from time zero to end of dosing interval (AUCtau) Part 1A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the curve from time zero to end of dosing interval (AUCtau) Part 2A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the curve from time zero to end of dosing interval (AUCtau) Part B
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 1A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part 2A
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) Part B
Time Frame: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
Safety Issue:
Description:To understand single and multiple dose parameters
Measure:Incidence and titers of anti-drug antibodies Part A
Time Frame: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
Safety Issue:
Description:To evaluate the immunogenicity of the drug
Measure:Incidence and titers of anti-drug antibodies Part B
Time Frame: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
Safety Issue:
Description:To evaluate the immunogenicity of the drug
Measure:Incidence and titers of neutralizing antibodies Part A
Time Frame: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
Safety Issue:
Description:To evaluate the immunogenicity of the drug
Measure:Incidence and titers of neutralizing antibodies Part B
Time Frame: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
Safety Issue:
Description:To evaluate the immunogenicity of the drug
Measure:Number of participant with objective response
Time Frame:Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months
Safety Issue:
Description:Document antitumor activity
Measure:Number of patients with progression free survival
Time Frame:Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months
Safety Issue:
Description:Document antitumor activity
Measure:HER2 expression level in patients with documented anti-tumor activity
Time Frame:Baseline and Cycle 3 Day 1 (for monotherapy: each cycle is 21 days; for combination therapy: each cycle is 28 days)
Safety Issue:
Description:Explore preliminary antitumor activity

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • HER2
  • PF-06804103
  • ADC
  • breast cancer
  • neoplasms
  • solid tumors
  • human epidermal growth receptor 2

Last Updated

July 31, 2020