Optimizing Body Mass Index (BMI) With TCMCB07, The Paradox Trial

This is a randomized, double-blind, placebo-controlled study of B07, administered daily by subcutaneous (SC) injection, in up to 100 patients with newly diagnosed metastatic colorectal cancer. This study will evaluate different doses of B07 on weight, body composition and BMI in patients with sub-optimal BMIs (18 to ≤ 29 kg/m2). Treatment will begin on the same day as the start of cancer chemotherapy and continue during the first 28 days of cytotoxic therapy with a goal of preserving muscle and fat mass, relative to placebo control.


Eligibility Criteria:
Inclusion Criteria:

1. Must be at least 18 years of age.
2. An ECOG performance status of ≤ 2.
3. Life expectancy of ≥ 9 months.
4. Able to eat and digest food normally. Patients with colostomies are allowed.
5. Must have newly diagnosed metastatic colorectal adenocarcinoma about to start first line chemotherapy.
6. Starting chemotherapy routines allowed are: FOLFOX, FOLFIRI, or FOLFIRINOX with or without bevacizumab, or other monoclonals or other FDA approved agents to be dosed every 2 weeks. The primary cancer therapy (dose, schedule, or drugs) may be changed as medically indicated.
7. Must have a BMI between 18 and ≤ 29 kg/m2.
8. Must be able and willing to safely self-inject daily or be injected by a care giver.
9. Must have measurable disease by RECIST 1.1 criteria.
10. Must have adequate end organ function as defined by:

    * Bone marrow function

      * ANC ≥ 1.5 × 109/L
      * Platelets ≥ 100 × 109/L
      * Hemoglobin ≥ 9 g/dL
    * Hepatic function

      * AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 × ULN
      * Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome
      * Albumin between 3.4 and 5.4 gm/dL or within institutional normal limits
    * Renal function

      o Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft and Gault equation See Appendix 2 \[Section 10.2\]).
    * Metabolic function o Normal hemoglobin A1c levels based on institutional normal limits
11. NT-Pro-BNP and Troponins (TnI, TnT) within institutional normal limits.
12. If a female of childbearing capacity, must have a negative pregnancy test within 2 weeks of starting treatment.
13. Fertile men and women must agree to use adequate contraception for the duration of the trial.
14. Willing and able to sign informed consent.

Exclusion Criteria:

1. Patients receiving second line or later systemic treatment for stage IV disease.
2. Patients with swallowing abnormalities, malabsorption syndromes, short or inflammatory bowel syndromes, or other conditions that in the Investigator's opinion could impair food consumption or metabolism.
3. History of weight loss surgery including gastric stapling, or bypass.
4. Unintentional weight loss ≥ 10% of usual body weight in 4 months prior to Screening or other weight loss considered significant by the Investigator.
5. Currently using any new agent designed to increase appetite or otherwise affect weight (increase or decrease).

   * THC containing agents (e.g., dronabinol, cannabis) or other weight promoting agents including androgenic compounds (e.g., testosterone, oxandrolone), dopamine antagonists, or megestrol acetate within the past 6 months is excluded. Chronic (\> 6 months) use is allowed for THC.
   * Newly prescribed glucocorticoids for less than four weeks at the time of Screening and whose weight is not yet stable are excluded. Stable (dose unchanged for 4 weeks or more) and low dose (\<4mg) corticosteroids are permissible, as are inhaled corticosteroids.
6. Chronic and ongoing use of corticosteroids at a dose of ≥5 mg of prednisone or equivalent per day.
7. History of bulimia or anorexia.
8. Pregnancy, lactation, or plans to become pregnant.
9. History of another malignancy except basal cell carcinoma of the skin, carcinoma in situ of the cervix or other noninvasive or indolent malignancy that has previously undergone potentially curative therapy.
10. Concurrent participation in any other clinical trial.
11. Patients with known brain or central nervous system (CNS) metastases.
12. Impaired cardiac function or significant cardiac issues including, but not limited to, any of the following:

    1. Greater than class II NYHA congestive heart failure
    2. Congenital long QT syndrome
    3. QTc \> 470 msec (as calculated by institution standards) confirmed by two ECGs ≥ 1-minute apart (interval corrected using \[Bazett's formula \[QTcB\])
    4. Unstable angina pectoris
    5. Acute myocardial infarction ≤ 6 months prior to study entry
13. Known hypersensitivity to B07 or its formulation.
14. Known diagnosis of HIV infection (HIV testing is not mandatory).
15. Active infection with Hepatitis B, Hepatitis C, or active systemic viral disease or active severe infection. Patients with a history of HIV regardless of viral load are excluded.
16. Unwilling or unable to comply with the protocol.
17. Any condition that, in the Investigator's opinion, would impair the patients' ability to participate in this study.