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Small Cell CarcinomaPhase 2NCT02489903

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

A Phase 2 study testing RRx-001, Cisplatin and Etoposide in people with Small Cell Carcinoma and Carcinoma, Non-Small-Cell Lung, run by EpicentRx, Inc. at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RRx-001, Cisplatin and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
139 participants
Where
10 sitesUnited States
Study dates
Jun 2015to 6 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.
Show all 24Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45267

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Henry Ford Allegiance Health

    Jackson, Michigan, 49201

  • Baptist Health

    Lexington, Kentucky, 40503

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Stanford University

    Palo Alto, California, 94304

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Washington University

    St Louis, Missouri, 63110

  • VA Connecticut Cancer Center

    West Haven, Connecticut, 06516

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
RRx-001, Cisplatin, Etoposide, Carboplatin, Irinotecan
Keywords
Epigenetics, resensitization, Platinum doublets, lung cancer, Ovarian epithelial cancer
Medical subject headings
Carcinoma, Small Cell, Carcinoma, Non-Small-Cell Lung, Neuroendocrine Tumors, Carcinoma, Ovarian Epithelial, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02489903
Study groupRoleWhat they receive
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).
Receives: Drug: RRx-001; Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin
Small Cell Lung Cancer (Arm 2)Active comparatorCarboplatin or cisplatin plus etoposide or irinotecan or vinorelbine until progression or intolerable toxicity
Receives: Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin; Drug: Irinotecan; Drug: 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).
Receives: Drug: RRx-001; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-Paclitaxel; Drug: 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).
Receives: Drug: RRx-001; Drug: Cisplatin; Drug: Etoposide; Drug: 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).
Receives: Drug: RRx-001; Drug: Carboplatin
Ovarian epithelial cancer (Arm 2)Active comparatorCarboplatin, Etoposide, Doxil, Gemcitabine or Vinorelbine or Taxane until progression or intolerable toxicity
Receives: Drug: Etoposide; Drug: Carboplatin; Drug: Vinorelbine; Drug: Doxil; Drug: Gemcitabine; Drug: Taxane

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    From 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.

    Measured: From start of treatment through death for up to 64 months from Start of Treatment.

Secondary outcomes (3)

  1. Overall Response Rate (ORR)

    Overall Response Rate (ORR) will be defined as the proportion of patients with a CR or a PR per RECIST v1.1 based upon the best response as assessed; confirmation of response was not required, assessed up to 49 months.

    Measured: Assessed up to 49 months

  2. Disease Control Rate (DCR)

    The percentage of patients who have achieved complete response, partial response and stable disease (as per RECIST v1.1), assessed up to 49 months.

    Measured: Assessed up to 49 months

  3. Progression Free Survival (PFS)

    Progression-free survival (PFS) will be defined as the elapsed time from the from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 49 months.

    Measured: Assessed up to 49 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2015 (estimated)
  2. Study startJun 2015
  3. Primary completion6 Dec 2021
  4. Study completion6 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
139 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02489903
Sponsor's protocol ID
RRx001-211-01
Status last verified
Feb 2025
First submitted
29 Jun 2015
Last updated
17 Mar 2025
Data monitoring committee
No

Publications

  • Tomita Y, Oronsky B, Abrouk N, Cabrales P, Reid TR, Lee MJ, Yuno A, Baker J, Lee S, Trepel JB. In small cell lung cancer patients treated with RRx-001, a downregulator of CD47, decreased expression of PD-L1 on circulating tumor cells significantly correlates with clinical benefit. Transl Lung Cancer Res. 2021 Jan;10(1):274-278. doi: 10.21037/tlcr-20-359.

    PubMed 33569311

  • Morgensztern D, Rose M, Waqar SN, Morris J, Ma PC, Reid T, Brzezniak CE, Zeman KG, Padmanabhan A, Hirth J, I Spira A, Trepel JB, Padda SK. RRx-001 followed by platinum plus etoposide in patients with previously treated small-cell lung cancer. Br J Cancer. 2019 Jul;121(3):211-217. doi: 10.1038/s41416-019-0504-8. Epub 2019 Jun 24.

    PubMed 31231122

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RRx-001, Cisplatin and Etoposide in people with Small Cell Carcinoma and Carcinoma, Non-Small-Cell Lung, run by EpicentRx, Inc. at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: From start of treatment through death for up to 64 months from Start of Treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02489903, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.

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