Study to Assess the Safety and Tolerability of Repeated Doses of an Investigational New Drug in Patients With Cancer and Cachexia.

A PHASE 1B, 12-WEEK, OPEN-LABEL STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS FOLLOWING REPEATED SUBCUTANEOUS ADMINISTRATIONS OF PF-06946860 IN PATIENTS WITH CANCER AND CACHEXIA

Study to assess the safety and tolerability of repeated doses of an investigational new drug in patients with cancer and cachexia.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Pancreatic Cancer; Cachexia; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: PF-06946860

Detailed Description

This 12-week open-label study will explore how PF-06946860 is tolerated, the effects of the study drug, the best dose for treatment and how participants with non-small cell lung, pancreatic or colorectal cancer and cachexia feel after receiving repeated subcutaneous dosing. During the 12-week treatment period, study drug will be administered subcutaneously every 3 weeks for a total of 5 doses. There is a 12-week follow-up period following the last dose of study drug. Additional assessments include:

• body weight measurements
• blood pressure and heart rate measurements
• Lumbar Skeletal Muscle Index (LSMI) by CT scan

• Blood samples:

  • to evaluate safety,
  • to measure the amount of the study drug in the blood,
  • to evaluate if the study drug causes an immune response,
  • to examine the effects of the study drug on levels of a specific cytokine,
  • and for exploratory samples for bio banking.
• Measure the impact of the study drug on appetite, nausea, vomiting, fatigue, physical function, and health-related quality of life with questionnaires.
• Measure the impact of study drug on physical activity using wearable digital sensors.
• To evaluate the effect of study drug on ability to complete anti-tumor treatment and survival in participants with cancer and cachexia.
• To evaluate tumor size.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Colorado
    • Grand Junction, Colorado, United States, 81501
      • SCL Health Cancer Centers of Colorado - St. Mary's Hospital and Regional Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • Lutheran Medical Center
  • Florida
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Healthcare Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc.
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland, PA
    • Germantown, Maryland, United States, 20874
      • American Oncology Partners of Maryland, PA
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented histologic or cytologic diagnosis of advanced metastatic NSCLC, advanced/unresectable pancreatic cancer, or metastatic colorectal cancer.
• Cachexia, defined by BMI <20 kg/m2 with involuntary weight loss of >2% within 6 months prior to screening or Involuntary weight loss of >5% within 6 months prior to screening irrespective of BMI or If medical record documentation is unavailable, patient's report will suffice to estimate involuntary body weight loss.;

• Will receive the following for non-small cell lung cancer:

  • a platinum + pemetrexed ± pembrolizumab or
  • a platinum + nab paclitaxel or paclitaxel ± pembrolizumab or
  • pembrolizumab alone

• Will receive the following for pancreatic cancer:

  • FOLFIRINOX or
  • Nab-Paclitaxel + Gemcitabine
  • Gemcitabine

• Will receive the following for colorectal cancer:

  • FOLFOX +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or
  • FOLFIRI +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or
  • FOLFOXIRI +/- Biologic (Bevacizumab or Cetuximab/Panitumumab) or
  • Pembrolizumab for MSI-H • Will be entering the study at the first or second cycle of their current course of anti-cancer treatment/ therapy.
• Adequate renal and liver function.
• Signed informed consent.

Exclusion Criteria:

• All other forms of cancers not specified above unless currently considered cured (>5 years without evidence of recurrence).
• Planned radiation therapy as part of the primary anti-tumor therapy regimen. However, localized radiation therapy for symptomatic relief is permitted
• Cachexia caused by other reasons: Severe COPD requiring use of home O2, heart failure or AIDS.
• known symptomatic brain metastases requiring steroids.
• Active hepatitis B or C virus.
• Confirmed positive HIV test.
• Current active reversible causes of decreased food intake.
• Receiving tube feedings or parenteral nutrition at Screening.
• Elevated blood pressure that cannot be controlled by medications.
• Women who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06946860; subcutaneous injection	Drug: PF-06946860; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. An AE was considered an TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs.	From Day 1 up to Week 24
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Participants with laboratory test abnormalities (without regard to baseline abnormality) that met pre-specified criteria included Hemoglobin< 0.8x lower limit of normal (LLN); Hematocrit< 0.8x LLN; Erythrocytes (Ery.)< 0.8x LLN; Ery. Mean Corpuscular Volume< 0.9x LLN; Leukocytes< 0.6x LLN; Lymphocytes< 0.8x LLN; Bilirubin> 1.5x upper limit of normal (ULN); Aspartate Aminotransferase> 3.0x ULN; Alkaline Phosphatase> 3.0x ULN; Protein< 0.8x LLN; Sodium< 0.95x LLN; Chloride< 0.9x LLN; Calcium< 0.9x LLN; Bicarbonate< 0.9x LLN; Glucose> 1.5x ULN; C Reactive Protein> 1.1x ULN; for urinalysis, Urine Glucose ≥1, Ketones ≥1, Urine Protein ≥1, Urine Hemoglobin ≥1, Urobilinogen ≥1, Nitrite ≥1, and Leukocyte ≥1 Esterase ≥1; Hyaline Casts >1/LPF.	From Day 1 up to Week 24
Number of Participants With Post-Baseline Vital Signs Abnormalities	Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg), supine SBP increase/decrease from baseline ≥30 mmHg; supine diastolic blood pressure (DBP) <50 mmHg, supine DBP increase/decrease from baseline ≥20 mmHg; supine pulse rate <40 beats per minute (bpm) or >120 bpm.	From Day 1 up to Week 24
Number of Participants With Post-Baseline Electrocardiogram (ECG) Abnormalities	ECG data (PR interval, QRS interval, QT interval, and QTcF) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥300 milliseconds (msec), percentage change ≥25/50%; QRS interval: value ≥140 msec, percentage change ≥50%; QT interval: value ≥500 msec; QTcF interval: 470< value ≤480 msec, 480< value ≤500 msec, value >500 msec, and 30< change ≤60 msec, change >60 msec.	From Day 1 up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Unbound Trough Concentrations (Ctrough) of PF-06946860	Ctrough was defined as the samples measured pre-dose at Weeks 3, 6, 9 and 12, and at Week 15. Serum unbound Ctrough was summarized by time and treatment group.	Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15
Serum Total Ctrough of PF-06946860	Ctrough was defined as the samples measured pre-dose at Weeks 3, 6, 9 and 12, and at Week 15. Serum total Ctrough was summarized by time and treatment group.	Pre-dose at Weeks 3, 6, 9 and 12, and at Week 15

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: February 19, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: cachexia, non-small cell lung cancer, pancreatic cancer; colorectal cancer, weight loss, anorexia, muscle loss, fatigue
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Nutrition Disorders; Body Weight; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Body Weight Changes; Lung Neoplasms; Pancreatic Diseases; Weight Loss; Thinness; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Wasting Syndrome; Cachexia
• Other Study ID Numbers: C3651009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No