This study is designed to explore the potential of the epigenetic agent RRx-001 to sensitize
patients who previously received and now have failed a platinum based doublet regimen.
RRx-001 is administered with autologous blood once weekly followed by or in combination with
reintroduction of platinum-based doublet therapy.
This is an open label, four 'cohort' study for administration of RRx-001 with autologous
blood once weekly followed by or in combination with reintroduction of platinum-based doublet
therapy according to the treatment schedule listed below. Small cell carcinoma and ovarian
cohort participants will be randomized to 1 of 2 treatment arms, respectively. Neuroendocrine
and NSCLC patients will be enrolled to single arms.
Participants with SCC will receive one of the following; RRx-001 followed by platinum doublet
chemotherapy or platinum based chemotherapy alone. HGNEC, RRx-001 followed by platinum
doublet chemotherapy. NSCLC, RRx-001 followed by platinum doublet chemotherapy. Participants
with Platinum Refractory/Resistant Ovarian and MMMT will receive one of the following,
RRx-001 followed by platinum doublet chemotherapy or chemotherapy alone.
Approximately 213 participants will be enrolled.
- 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
- 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
- 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
- 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