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

NCT02489903 | Completed Phase 2 Results

• 1 other identifier: RRx001-211-01
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 10

Brief 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. RRx-001 is administered with autologous blood once weekly followed by or in combination with reintroduction of platinum-based doublet therapy.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Assessed up to 49 months

• Disease Control Rate (DCR)

  Assessed up to 49 months

• Progression Free Survival (PFS)

  Assessed up to 49 months

Study Arms (6)

Small Cell Lung Cancer (Arm 1)

EXPERIMENTAL

RRx-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).

Drug: RRx-001; Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin

Small Cell Lung Cancer (Arm 2)

ACTIVE COMPARATOR

Carboplatin or cisplatin plus etoposide or irinotecan or vinorelbine until progression or intolerable toxicity

Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin; Drug: Irinotecan; Drug: Vinorelbine

Non Small Cell Lung Cancer

EXPERIMENTAL

RRx-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).

Drug: RRx-001; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-Paclitaxel; Drug: Pemetrexed

Neuroendocrine tumors

EXPERIMENTAL

RRx-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).

Drug: RRx-001; Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin

Ovarian epithelial cancer (Arm 1)

EXPERIMENTAL

RRx-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).

Drug: RRx-001; Drug: Carboplatin

Ovarian epithelial cancer (Arm 2)

ACTIVE COMPARATOR

Carboplatin, Etoposide, Doxil, Gemcitabine or Vinorelbine or Taxane until progression or intolerable toxicity

Drug: Etoposide; Drug: Carboplatin; Drug: Vinorelbine; Drug: Doxil; Drug: Gemcitabine; Drug: Taxane

Interventions

RRx-001 DRUG

Neuroendocrine tumors; Non Small Cell Lung Cancer; Ovarian epithelial cancer (Arm 1); Small Cell Lung Cancer (Arm 1)

Cisplatin DRUG

Neuroendocrine tumors; Non Small Cell Lung Cancer; Small Cell Lung Cancer (Arm 1); Small Cell Lung Cancer (Arm 2)

Etoposide DRUG

Neuroendocrine tumors; Ovarian epithelial cancer (Arm 2); Small Cell Lung Cancer (Arm 1); Small Cell Lung Cancer (Arm 2)

Carboplatin DRUG

Neuroendocrine tumors; Non Small Cell Lung Cancer; Ovarian epithelial cancer (Arm 1); Ovarian epithelial cancer (Arm 2); Small Cell Lung Cancer (Arm 1); Small Cell Lung Cancer (Arm 2)

Irinotecan DRUG

Small Cell Lung Cancer (Arm 2)

Vinorelbine DRUG

Ovarian epithelial cancer (Arm 2); Small Cell Lung Cancer (Arm 2)

Doxil DRUG

Ovarian epithelial cancer (Arm 2)

Gemcitabine DRUG

Ovarian epithelial cancer (Arm 2)

Taxane DRUG

Ovarian epithelial cancer (Arm 2)

Paclitaxel DRUG

Non Small Cell Lung Cancer

Nab-Paclitaxel DRUG

Non Small Cell Lung Cancer

Pemetrexed DRUG

Non Small Cell Lung Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (10)

Stanford University

Palo Alto, California, 94304, United States

Location

VA Connecticut Cancer Center

West Haven, Connecticut, 06516, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Baptist Health

Lexington, Kentucky, 40503, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Henry Ford Allegiance Health

Jackson, Michigan, 49201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Publications (2)

• 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.

  PMID: 33569311 DERIVED

• 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.

  PMID: 31231122 DERIVED

MeSH Terms

Conditions

Carcinoma, Small Cell; Carcinoma, Non-Small-Cell Lung; Neuroendocrine Tumors; Carcinoma, Ovarian Epithelial; Lung Neoplasms

Interventions

RRx-001; Cisplatin; Etoposide; Carboplatin; Irinotecan; Vinorelbine; liposomal doxorubicin; Gemcitabine; taxane; Paclitaxel; 130-nm albumin-bound paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Bryan Oronsky
• Organization: EpicentRx, Inc

mstirn@epicentrx.com

858-229-1062

Study Officials

• Bryan Oronsky, MD, PhD

  EpicentRx, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2015
• First Posted: July 3, 2015
• Study Start: June 1, 2015
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-02

Locations

US (10)