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

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ClinicalTrials.gov Identifier: NCT03284723
Recruitment Status : Completed
First Posted : September 15, 2017
Last Update Posted : September 24, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: PF-06804103 Drug: PF-06804103 + Palbociclib +Letrozole Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 1, 2017
Actual Primary Completion Date : August 31, 2021
Actual Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06804103
Study Treatment
Drug: PF-06804103
Dose Escalation Part - 1A Dose Expansion Part - 2A

Experimental: PF-06804103+Combination Regimen
Study Treatment
Drug: PF-06804103 + Palbociclib +Letrozole
Dose Escalation - Part 1B Dose Expansion - Part 2B




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

  2. Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Part 1 and Part 2: Baseline through LSLV (up to approximately 2 years) ]
    Assessment of all available safety data in order to determine the safety and tolerability of monotherapy and combination therapy

  3. Number of participant with objective response [ Time Frame: Part 2: Baseline through LSLV (up to approximately 2 years) ]
    To investigate preliminary antitumor activity

  4. Duration of Response (DR) [ Time Frame: Part 2: Baseline through LSLV (up to approximately 2 years) ]
    To investigate preliminary antitumor activity

  5. Progression-Free Survival (PFS) [ Time Frame: Part 2: Baseline through LSLV (up to approximately 2 years) ]
    To investigate preliminary antitumor activity

  6. Time to Tumor Progression (TTP) [ Time Frame: Part 2: Baseline through LSLV (up to approximately 2 years) ]
    To investigate preliminary antitumor activity


Secondary Outcome Measures :
  1. 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 ]
    To understand single and multiple dose parameters

  2. 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 ]
    To understand single and multiple dose parameters

  3. 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 ]
    To understand single and multiple dose parameters

  4. 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 ]
    To understand single and multiple dose parameters

  5. 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 ]
    To understand single and multiple dose parameters

  6. 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 ]
    To understand single and multiple dose parameters

  7. 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 ]
    To understand single and multiple dose parameters

  8. 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 ]
    To understand single and multiple dose parameters

  9. 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 ]
    To understand single and multiple dose parameters

  10. 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 ]
    To understand single and multiple dose parameters

  11. 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 ]
    To understand single and multiple dose parameters

  12. 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 ]
    To understand single and multiple dose parameters

  13. 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 ]
    To evaluate the immunogenicity of the drug

  14. 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 ]
    To evaluate the immunogenicity of the drug

  15. 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 ]
    To evaluate the immunogenicity of the drug

  16. 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 ]
    To evaluate the immunogenicity of the drug

  17. 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 ]
    Document antitumor activity

  18. Progression-Free Survival (PFS) [ Time Frame: Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months ]
    Document antitumor activity

  19. 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) ]
    Explore preliminary antitumor activity

  20. Duration of Response (DR) [ Time Frame: Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months ]
    Document antitumor activity

  21. Time to Tumor Progression (TTP) [ Time Frame: Baseline and every 6 weeks (monotherapy) or every 8 weeks (combination therapy) until disease progression, unacceptable toxicity, or up to 24 months ]
    Document antitumor activity



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03284723


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03284723    
Other Study ID Numbers: C0541001
2017-002538-22 ( EudraCT Number )
First Posted: September 15, 2017    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
HER2
PF-06804103
ADC
breast cancer
neoplasms
solid tumors
human epidermal growth receptor 2
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors