Ruxolitinib for Cancer Cachexia

• Status: Not yet recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

To assess toxicity with use of ruxolitinib in NSCLC cachexia patients; to associate levels of JAK/STAT signaling in blood, adipose, and muscle pre- and post-ruxolitinib treatment with changes in cachexia and anorexia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Puneeth Iyengar
• Collaborator: Incyte Corporation

Criteria

Inclusion Criteria:

1. Male or female subjects at least 18 years of age;

2. Ability to understand and the willingness to sign a written informed consent;

3. Histological or biopsy proven Non-Small Cell Lung Cancer (squamous or non-squamous) .

4. ECOG performance status of 0-2

5. Patients with evidence of cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (>5% weight loss over the preceding 6 months prior to diagnosis).

6. Patients with evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to <=5% weight loss over the preceding 6 months prior to diagnosis).

7. Any de novo stage IV NSCLC disease diagnosis as defined by AJCC 8th edition staging. Staged with PET/CT, MRI brain, or other acceptable staging tool; measurable disease as defined by RECIST 1.1

8. Adequate end-organ function, based on routine clinical and laboratory workup and institutional guidelines, as determined by oncology team offering patient standard of care therapy, including:

1. ANC >1,000 cells/µl, Platelets ≥ 50,000 cells/µl, Hemoglobin ≥ 8.0 g/dl;

2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 45 ml/min;

3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN;

4. International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, if values are within the intended therapeutic range.

9. Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control,abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

a. Has not undergone a hysterectomy or bilateral oophorectomy

b. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) .

10. Male subjects who are surgically sterile or are using a medically acceptable form of contraception for 90 days following the completion of therapy.

11. Life expectancy anticipated to be 6 months or greater.

12 . No prior therapy for advanced lung cancer.

Exclusion Criteria:

1. Subjects with confirmed stage I-III NSCLC;

2. Patients whose tumors have actionable mutations treatable with targeted therapies;

3. Patients with no evidence of cancer cachexia, defined by the International Cancer Cachexia Consensus Definition (>5% weight loss over the preceding 6 months prior to diagnosis);

4. Patients with no evidence of cancer pre-cachexia, defined by the International Cancer Cachexia Consensus Definition (0 to <=5% weight loss over the preceding 6 months prior to diagnosis);

5. Active malignancy other than lung cancer that requires concurrent treatment other than hormonal therapy and is deemed by the treating physicians to be likely to affect the subject's survival duration;

6. Subjects who have not recovered or have disease control from prior treatment-related to toxicities judged by treating physician;

7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study;

8. Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements;

9. Inadequate liver or renal function, if out of the acceptable ranges of the inclusion criteria;

10. Significant bacterial, fungal, parasitic, or viral infection requiring treatment;

11. Previous treatment with a JAK inhibitor;

12. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of ruxolitinib;

13. Females who are pregnant, breast-feeding or plan to become pregnant;

14. Participation in other clinical trials either to treat diagnosed lung or other cancers (patients on registry trials are eligible);

15. Requirement for treatment with drugs that may, in the judgment of the treating investigator, create a risk for a precipitous change in patient's health;

16. Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study;

17. Life expectancy of less than 6 months;

18. Prior therapy for the newly diagnosed advanced lung cancer.