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Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (CDK4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04557449
Recruitment Status : Not yet recruiting
First Posted : September 21, 2020
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

This is a Phase 1, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.

In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D). In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).

Part 1B and Part 1C may be enrolled and conducted in parallel at the completion of Part 1A.


Condition or disease Intervention/treatment Phase
Liposarcoma CRC Prostate Cancer Breast Neoplasms Adenocarcinoma of Lung Solid Tumors Drug: PF-07220060 Combination Product: Letrozole Combination Product: Fulvestrant Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1/1B STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : September 4, 2024
Estimated Study Completion Date : September 4, 2024


Arm Intervention/treatment
Experimental: Monotherapy Escalation Arm 1
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: Monotherapy Escalation Arm 2
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: Monotherapy Escalation Arm 3
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: Monotherapy Escalation Arm 4
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1B Combination Dose Finding Arm 1
PF-07220060 with Letrozole combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Letrozole
Endocrine Therapy
Other Name: Femara

Experimental: 1B Combination Dose Finding Arm 2
PF-07220060 with Letrozole Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Letrozole
Endocrine Therapy
Other Name: Femara

Experimental: 1C Combination Dose Finding Arm 1
PF-07220060 with Fulvestrant Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Fulvestrant
Endocrine Therapy
Other Name: Faslodex

Experimental: 1C Combination Dose Finding Arm 2
PF-07220060 with Fulvestrant Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Fulvestrant
Endocrine Therapy
Other Name: Faslodex




Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities in the Dose Escalation Portion [ Time Frame: Baseline up to day 28 of Cycle 1. ]
  2. Incidence of clinically significant AEs [ Time Frame: Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days ]
    Adverse Events

  3. Incidence of clinically significant laboratory assessments [ Time Frame: Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months ]
    safety laboratory abnormalities

  4. Incidence of clinically significant abnormal vital and ECG parameters [ Time Frame: Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days) ]
    vital signs and heart rate corrected QT interval


Secondary Outcome Measures :
  1. Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  2. Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  3. Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  4. Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion [ Time Frame: Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  5. Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  6. Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  7. Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  8. Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  9. Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  10. Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  11. Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  12. Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  13. Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  14. Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060

  15. Tumor Response observed in participants in Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  16. Duration of Response (DOR) in participants enrolled in the Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  17. Progression Free Survival (PFS) observed in participants in the Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  18. Time to Progression (TTP) observed in participants enrolled in the Dose Escalation and Dose Finding portion [ Time Frame: baseline up to approximately 24 months ]
  19. Overall Survival observed in participants enrolled in the Dose Expansion Arms [ Time Frame: baseline up to approximately 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

  • Disease Characteristics - Breast Cancer (Part 1A, Part 1B and Part 1C)
  • Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer (2L + with prior CDK 4/6) locally advance or metastatic breast cancer. Participants should have received at least 1 line of SOC, including CDK4/6 inhibitor therapy, or at least 1 line of anti-endocrine therapy in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease
  • Part 1A only: Refractory HR-positive (HR+), Human Epidermal Growth Factor Receptor 2 Positive (HER2+) breast cancer
  • Evaluable lesion (including skin or bone lesion only)
  • Disease Characteristics - Part 1A: Tumors other than BC
  • Participants with advanced or metastatic disease
  • Participants with histological or cytological diagnosis of adenocarcinoma of NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests, that is resistant to at least 2 lines of standard systemic therapy for advanced or recurrent disease or for which no standard therapy is available
  • Participants must not be eligible to undergo therapy with curative intent (surgery or radiation therapy with or without chemotherapy

General Inclusion Criteria

  • All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
  • Adequate renal, liver, and bone marrow function

Exclusion Criteria:

  • Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
  • Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
  • Major surgery or radiation within 4 weeks prior to study intervention
  • Last anti-cancer treatment within 2 weeks prior to study intervention
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
  • Pregnant or breastfeeding female participant
  • Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease

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): NCT04557449


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Texas
The University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
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: NCT04557449    
Other Study ID Numbers: C4391001
2020-002938-33 ( EudraCT Number )
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
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
Additional relevant MeSH terms:
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Breast Neoplasms
Liposarcoma
Adenocarcinoma of Lung
Neoplasms by Site
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Diseases
Skin Diseases
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Letrozole
Fulvestrant
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
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists