RRx-001 in Lung Cancer, Ovarian Cancer and Neuroendocrine Tumors Prior to Re-administration of Platinum Based Doublet Regimens (QUADRUPLE THREAT)

Inclusion Criteria

   - Patients must have histologically or cytologically confirmed advanced or metastatic:

      - Resistant/Refractory Small Cell Carcinoma (SCC) patients in 3rd line or beyond
      that have previously received platinum or patients in 2nd line with
      platinum-refractory or platinum-resistant disease

      - EGFR mutated non-small cell lung cancer (NSCLC) that has previously received a
      first line platinum doublet and all applicable EGFR TKIs

      - Epithelial Ovarian Cancer (EOC), fallopian tube or primary peritoneal cancer and
      Malignant Mixed Mullerian Tumor (MMMT) of the ovary or uterus. Excludes other
      non-epithelial ovarian tumors and ovarian tumors with low malignant potential.
      Patients must have previously received a platinum based regimen for
      advanced/metastatic disease or have platinum resistant or refractory disease
      defined as relapse within 6 months. EOC - specific criteria: Patients who
      progress or have stable disease during first-line treatment or who relapse within
      1 month are considered to be 'platinum-refractory'. Patients who respond to
      primary treatment and relapse within 6 months are considered
      'platinum-resistant', and patients who relapse more than 6 months after
      completion of initial therapy are characterized as 'platinum-sensitive'. Patients
      who relapse 6-12 months following the end of their initial regimen are classified
      as 'partially sensitive'. Platinum sensitive patients may be enrolled but must
      have failed or declined all other lines of FDA approved therapy

      - High-Grade Neuroendocrine Carcinoma (HGNEC), any organ of origin, including a
      pathology of neuroendocrine features, in patients previously been treated with
      chemotherapy Although neuroendocrine tumors may be classified differently based
      on organ of origin, in the context of this protocol they are defined as high
      grade on the basis of either

         1. Aggressive clinical behavior requiring previous treatment with chemotherapy
         even if histologic features such as the Ki67 index or mitotic rate
         corresponds with low or intermediate grade.

         2. Histologic features: (a) Neuroendocrine tumors of lung origin are considered
         high grade if in any part of the tumors, there are >10 mitoses/2mm2 or 10
         high power field (HPF). Large zones of necrosis are usually present. This
         includes small cell lung carcinoma and large cell neuroendocrine lung
         carcinoma. [SCLC will not enroll in the HGNEC cohort.] (b)Neuroendocrine
         tumors of gastroenteropancreatic origin are considered high grade if in any
         part of the tumors there are either >20 mitoses/2mm2 or 10 high power field
         (HPF) OR Ki67.

   - Radiographically measurable disease by RECIST v1.1

   - A washout period of 3-weeks from last treatment.

   - Patients must have previously received a platinum based regimen for
   advanced/metastatic disease and progressed or have platinum resistant or refractory
   disease defined as relapse within 6 months.

   - Age ≥18 years.

   - Life expectancy of ≥12 weeks.

   - ECOG performance status 0-2.

   - Participants must have adequate organ and marrow function as defined below both prior
   to administration of RRx-001 and prior to administration of platinum doublet based
   regimen:

      - Absolute neutrophil count ≥1,500/mcL

      - Platelets ≥100,000/mcL (non-transfused platelet count)

      - Hemoglobin ≥9 g/dL (transfused Hgb allowed)

      - Creatinine ≤1.5 x the upper limit of normal

      - Total bilirubin ≤2.0 x the upper limit of normal or <3.0 xULN if patient has a
      history of Gilbert's syndrome

      - AST (SGOT)/ALT (SGPT) ≤5 X institutional upper limit of normal if with liver
      metastases; ≤2.5 X ULN if no liver metastases

   - Patient must consent to the access, review and analysis of previous medical and cancer
   history, including tumor archival tissue (if available) and imaging data by the
   sponsor or a third party nominated by the sponsor.

   - Ability to understand and sign a written informed consent document.

   - Women of child-bearing potential and men with partners of child-bearing potential 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.

      - Note: A woman of child-bearing potential is any female (regardless of sexual
      orientation, having undergone a tubal ligation, or remaining celibate by choice)
      who meets the following criteria: Has not undergone a hysterectomy or bilateral
      oophorectomy; or Has not been postmenopausal for at least 12 consecutive months

Exclusion Criteria

   - Receiving concurrent investigational therapy

   - Symptomatic central nervous system metastasis (e.g., patients requiring increasing
   doses of steroids)

   - History of needing to permanently discontinue prior platinum doublet-based regimen for
   toxicity (e.g., cisplatin causing renal impairment, ototoxicity, or severe
   neuropathy).

   - Known severe hypersensitivity to the platinum agent (i.e., carboplatin or cisplatin)
   or prior partner of platinum agent (i.e., etoposide for SCC and HGNEC; nab-paclitaxel,
   paclitaxel, or pemetrexed for NSCLC; paclitaxel, pegylated liposomal doxorubicin,
   docetaxel or gemcitabine for ovarian) planned for the platinum therapy period. If the
   patient has had prior hypersensitivity reaction to the drug partner of platinum, a
   patient may enroll as long as it is acceptable to treat with platinum and one of the
   alternative chemotherapy partner agents.

   - Any significant medical diseases or conditions, as assessed by the investigators and
   sponsor that would substantially increase the medical risks of participating in this
   study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial
   infarction within 6 months of study, severe chronic pulmonary disease or active
   uncontrolled infection, uncontrolled or clinically relevant pulmonary edema).

   - Pregnant or nursing