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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Pancreatic Cancer, Cachexia, Non-Small-Cell Lung Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: PF-06946860


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06946860<br>subcutaneous injection | Drug: PF-06946860<br>* subcutaneous injection<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cachexia, non-small cell lung cancer, pancreatic cancer, colorectal cancer, weight loss, anorexia, muscle loss, fatigue