NR in Chemo-induced Peripheral Neuropathy
Condition: Chemotherapy-induced Peripheral Neuropathy; Breast Cancer Metastatic; Platinum-resistant Recurrent Ovarian Cancer; Head and Neck Cancer Stage IV; Endometrial Cancer Stage IV
MeSH terms: Endometrial Neoplasms; Peripheral Nervous System Diseases
Intervention: Nicotinamide Riboside
Intervention description: Capsule
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: All subjects with stage IV breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer will receive 300 mg NIAGEN®) daily for one week followed by dose escalation to 1000 mg daily for 11 weeks upon reporting the development of grade 1 sensory neuropathy. Those presenting with a residual sensory neuropathy of ≤ 2 as a result of prior chemotherapy will also be enrolled.
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: paclitaxel; nicotinamide riboside; NIAGEN; nab-paclitaxel

Summary:

      The purpose of this single-arm phase II trial is to determine whether nicotinamide riboside
      (NIAGEN®) prevents the progression of peripheral sensory neuropathy in patients receiving
      infusions of paclitaxel or nab-paclitaxel for the treatment of metastatic breast cancer or
      recurrent platinum-resistant ovarian, endometrial, peritoneal, fallopian tube cancer or
      metastatic head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be able to give written informed consent and HIPAA authorization

          -  Be 18 to 85 years old

          -  Have been diagnosed with stage IV breast cancer of any type, platinum-resistant
             recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or
             platinum-resistant recurrent or metastatic head and neck cancer and are anticipated to
             survive for at least three months

          -  Have an ECOG Performance Status of 0-2

          -  Able to take medication orally - up to four capsules in the morning (am) and four
             capsules in the evening (pm).

          -  Be undergoing infusions of paclitaxel or nab-paclitaxel for treatment of breast
             cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian
             tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer and be
             determined to have at least a grade 1 neuropathy based on the CTCAE version 4.03
             guidelines for peripheral sensory neuropathy. Breast cancer patients may also be
             treated concomitantly with monoclonal antibodies to HER2 such as trastuzumab
             (Herceptin) and pertuzumab (Perjeta). Patients with platinum-resistant ovarian,
             peritoneal, endometrial, or fallopian tube cancer or platinum-resistant recurrent or
             metastatic head and neck cancer may also be treated concomitantly with a vascular
             endothelial growth receptor 2 inhibitor such as bevacizumab (Avastin) or a checkpoint
             inhibitor.

          -  Females must be either postmenopausal for at least 1 year or surgically sterile for at
             least 6 weeks. Females of childbearing potential must have a negative pregnancy test
             at screening to be eligible for study participation, and agree to take appropriate
             precautions to avoid pregnancy from screening through follow-up.

          -  Males must agree to take appropriate precautions to avoid fathering a child from
             screening through follow-up. The following methods have been determined to be more
             than 99% effective (<1% failure rate per year when used consistently and correctly)
             and are permitted under this protocol for use by the patient and his/her partner:

               -  Complete abstinence from sexual intercourse when this is in line with the
                  preferred and usual lifestyle of the patient

               -  Double barrier methods including condom with spermicide in conjunction with use
                  of an intrauterine device or condom with spermicide in conjunction with use of a
                  diaphragm

          -  Surgical sterilization (bilateral oopherectomy with or without hysterectomy, tubal
             ligation or vasectomy) at least 6 weeks prior to taking study treatment. In the case
             of oophorectomy alone, only when the reproductive status of the woman has been
             confirmed by follow-up levels of luteinizing hormone (LH), follicle-stimulating
             hormone (FSH), and/or estradiol.

        Non-hormonal intrauterine device used as directed by provider placing this is also
        acceptable.

        Exclusion Criteria:

          -  Pre-existent peripheral neuropathy that is unrelated to chemotherapy

          -  Pre-existent chemotherapy-induced peripheral neuropathy greater than grade 2

          -  Known metastases to the brain, spinal cord or peripheral nerves, or leptomeningeal
             disease

          -  Concurrent administration of a poly (ADP-Ribose) polymerase inhibitor (e.g. olaparib,
             rucaparib)

          -  Concurrent administration of a platinum-based chemotherapy

          -  Diabetes requiring management by medication

          -  Diabetes managed by medication

          -  Neutrophils < 1,000 cells/m3

          -  Hemoglobin < 8.0 g/dcl

          -  Platelets < 100,000 cells/m3

          -  Creatinine clearance < 30 ml/min

          -  AST or ALT values > 2.5 X upper limits of normal

          -  Total bilirubin > 2.0 X upper limits of normal

          -  Heavy alcohol use defined at > 8 drinks/week by women or 12 drinks/week by men

          -  Chronic pain greater than 3 months duration within the past year.

          -  Severe psychiatric illness

          -  Pregnancy

          -  Current imprisonment

          -  Limitations of self-expression, defined as an inability to answer questions posed by
             physicians, nurses, care-givers, or other members of the investigative team or an
             inability to describe somatosensations.

          -  Known HIV, not on therapy

          -  Regular use of nutritional supplements that contain nicotinamide or NIAGEN® within the
             previous 30 days

          -  Use of duloxetine (Cymbalta®) within the previous 30 days

          -  Pancreatic insufficiency requiring exocrine enzyme replacement therapy

          -  GI conditions where malabsorption of B complex vitamins is known to occur.

          -  Known allergy to Cremophor vehicle used to deliver paclitaxel in its Taxol formulation

          -  Breastfeeding