Clinical Trials /

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

NCT02489903

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Neuroendocrine Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinosarcoma
  • Ovarian Epithelial Tumor
  • Primary Peritoneal Carcinoma
  • Small Cell Lung Carcinoma
  • Uterine Carcinosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: RRx-001 in Lung Cancer, Ovarian Cancer and Neuroendocrine Tumors Prior to Re-administration of Platinum Based Doublet Regimens (QUADRUPLE THREAT)
  • Official Title: A Phase II Study of RRx-001 in Platinum Refractory/Resistant Small Cell Carcinoma, EGFR TKI Resistant EGFR+ T790M Negative Non-Small Cell Lung Cancer, High Grade Neuroendocrine Tumors and Resistant/Refractory Ovarian Cancer Prior to Re-administration of Platinum Based Doublet Regimens (QUADRUPLE THREAT)

Clinical Trial IDs

  • ORG STUDY ID: RRx001-211-01
  • NCT ID: NCT02489903

Conditions

  • Small Cell Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Neuroendocrine Tumors
  • Ovarian Epithelial Cancer

Interventions

DrugSynonymsArms
RRx-001Small Cell Lung Cancer (Arm 1)
CisplatinSmall Cell Lung Cancer (Arm 1)
EtoposideSmall Cell Lung Cancer (Arm 1)
CarboplatinSmall Cell Lung Cancer (Arm 1)
IrinotecanSmall Cell Lung Cancer (Arm 2)
VinorelbineSmall Cell Lung Cancer (Arm 2)
DoxilOvarian epithelial cancer (Arm 2)
GemcitabineOvarian epithelial cancer (Arm 2)
TaxaneOvarian epithelial cancer (Arm 2)
PaclitaxelNon Small Cell Lung Cancer
Nab-PaclitaxelNon Small Cell Lung Cancer
PemetrexedNon Small Cell Lung Cancer

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Small Cell Lung Cancer (Arm 1)ExperimentalRRx-001 weekly for 3 weeks followed by up to 4 cycles of carboplatin or cisplatin plus etoposide and then RRx-001 and carboplatin or cisplatin (for patients with stable disease (SD) or better at discontinuation of platinum).
  • RRx-001
  • Cisplatin
  • Etoposide
  • Carboplatin
Small Cell Lung Cancer (Arm 2)Active ComparatorCarboplatin or cisplatin plus etoposide or irinotecan or vinorelbine until progression or intolerable toxicity
  • Cisplatin
  • Etoposide
  • Carboplatin
  • Irinotecan
  • Vinorelbine
Non Small Cell Lung CancerExperimentalRRx-001 weekly for 3 weeks followed by up to 6 cycles of cisplatin or carboplatin plus paclitaxel or nab-paclitaxel or pemetrexed and then RRx-001 maintenance (for patients with stable disease or better at discontinuation of platinum).
  • RRx-001
  • Cisplatin
  • Carboplatin
  • Paclitaxel
  • Nab-Paclitaxel
  • Pemetrexed
Neuroendocrine tumorsExperimentalRRx-001 weekly until progression followed by up to 6 cycles of carboplatin or cisplatin plus etoposide and then RRx-001 maintenance (for patients with stable disease or better at discontinuation of platinum).
  • RRx-001
  • Cisplatin
  • Etoposide
  • Carboplatin
Ovarian epithelial cancer (Arm 1)ExperimentalRRx-001 weekly for 2 weeks followed by 2 cycles of Carboplatin chemotherapy and then RRx-001/Carboplatin maintenance (for patients with stable disease or better at discontinuation of platinum).
  • RRx-001
  • Carboplatin
Ovarian epithelial cancer (Arm 2)Active ComparatorCarboplatin, Etoposide, Doxil, Gemcitabine or Vinorelbine or Taxane until progression or intolerable toxicity
  • Etoposide
  • Carboplatin
  • Vinorelbine
  • Doxil
  • Gemcitabine
  • Taxane

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:up to one year
Safety Issue:
Description:the time from enrollment until the time of death from any cause or last follow-up. Patients will be followed clinically as outlined in the treatment schedule and will be followed off study for death.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:12 weeks
Safety Issue:
Description:The proportion of patients who achieve a reduction in the sum of target lesions by 30% following the re-administration of chemotherapy. Radiographic assessment of disease burden will be evaluated by CT and disease RR will be documented using RECIST v1.1.
Measure:Disease Control Rate (DCR)
Time Frame:12weeks
Safety Issue:
Description:The percentage of patients who have achieved complete response, partial response and stable disease (as per RECIST v1.1).
Measure:Progression Free Survival (PFS)
Time Frame:12 weeks
Safety Issue:
Description:the time from enrollment to the time of the first radiographic documentation of objective progression as defined by RECIST v1.1 or death from any cause.
Measure:Number of Participants with Adverse Events as a Measure of Safety and Tolerability of platinum doublet therapy post RRx-001
Time Frame:12 weeks
Safety Issue:
Description:
Measure:Changes in the level of serum biomarkers will be calculated and treatment samples will be compared to baseline samples using one-sample tests (e.g., paired t test or Wilcoxon signed rank test).
Time Frame:12 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EpicentRx, Inc.

Trial Keywords

  • Epigenetics
  • resensitization
  • Platinum doublets
  • lung cancer
  • Ovarian epithelial cancer

Last Updated

November 13, 2019