Malignant Solid Tumor, Lymphomas
Conditions
Keywords
Advanced Solid Tumors, Lymphomas, Safety, Blood flow, Nitric oxide, Cancer, Dynamic contrast enhanced MRI (DCE-MRI), Contrast Enhanced Ultrasound (CEUS)
Brief summary
The purpose of this study is to evaluate the safety and pharmacokinetic profile of RRx-001 for injection in subjects with advanced solid tumors or lymphomas for which there are no currently accepted curative therapies. This study will also conduct an exploratory evaluation of objective tumor response using CT or MRI.
Detailed description
The DINAMIC (DINitroazetidines As Medications In Cancer) trial represents a provascular approach to temporarily change tumor blood flow and oxygenation. Blood supply to most tumors is poor, causing parts of tumors to have a low oxygen content which promotes aggressiveness and metastasis. The DINAMIC trial uses specific imaging techniques (including ultrasound), biopsy, and breath analysis to provide an early assessment of therapeutic activity.
Interventions
DRUGRRx-001
Dose level 1 (10 mg/m2)
Sponsors
EpicentRx, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is male or female, aged at least 18 years. * Subject has a histologically or cytologically confirmed diagnosis of an advanced, malignant, incurable solid tumor(s) or lymphoma that is metastatic and/or unresectable and/or for which standard curative measures either are not applicable, or do not exist, or are no longer effective. Subjects with curative treatment options are not eligible for the protocol. * Subject is not receiving any active treatment for his/her malignancy (except for prostate cancer subjects receiving luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens such as: Flutamide, Dutasteride, and Finasteride). * Subject's Eastern Cooperative Group (ECOG) performance status is 0, 1 or 2 at Screening. * Subject has acceptable liver function at Screening * Subject has a normal serum creatinine. * Subject has acceptable hematologic status at Screening * Female subjects of childbearing potential (i.e., women who have not been surgically sterilized or have not been post-menopausal for at least one year), and male subjects with partners of childbearing potential, must agree to use medically acceptable methods of contraception beginning on Study Day 1 and continuing until at least four weeks after administration of the subject's final dose of RRx-001.
Exclusion criteria
* Impaired cardiac function that in the opinion of the Investigator could interfere with the conduct of the study or could put the subject at unacceptable risk. * Right-to-left, bidirectional, or transient right-to-left cardiac shunts. * Subjects with a history of acute cerebral infarction or transient ischemic attack within 90 days prior to Study Day 1. * Acute myocardial infarction or acute coronary syndromes less than one year prior to enrollment. * Serious ventricular arrythmias or high risk for arrhythmias due to prolongation of the QT interval. * Subjects who experienced a major surgery, radiotherapy, or immunotherapy within the last 21 days prior to Study Day 1 (limited palliative radiation is allowed within 14 days prior to Study Day 1). * Chemotherapy regimens with delayed toxicity within the 28 days prior to Study Day 1 (except for nitrosourea or mitomycin C treatments within 42 days prior to Study Day 1). * Chemotherapy regimens given continuously or on a weekly basis that Investigator believes to have a limited potential for delayed toxicity within 14 days prior to Study Day 1. * Use of an investigational anti-cancer drug within 42 days prior to Study Day 1. * Subject has symptomatic and/or untreated central nervous system metastases and/or intracranial hypertension. * Subject has a known history of an active and/or an uncontrolled infection with hepatitis A or hepatitis B. * Subject with a known history of a positive HIV status. * Subjects with pulmonary edema. * Subjects with respiratory failure * Subjects with severe emphysema, pulmonary emboli, pulmonary fibrosis or other conditions that cause pulmonary hypertension due to compromised pulmonary arterial vasculature. * Subjects with Raynaud's syndrome. * Subjects with a serious co-morbid medical condition. * If female, subject is pregnant and/or breastfeeding. * Any subject with congenital or acquired methemoglobinemia. * Any subject with a history of inherited anemia or hemoglobinopathy including but not limited to hereditary spherocytosis, hereditary elliptocytosis, hereditary ovalocytosis,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Had an Adverse Events | From time of receiving a dose of RRx-001 through 92 days | The total number of patients who experienced at least one adverse event while receiving treatment. |
Countries
United States
Participant flow
Recruitment details
Between Oct 10, 2011, and March 18, 2013, we screened 26 patients from the University of California- San Diego Moores Cancer Center, La Jolla, CA, USA, and the Sarah Cannon Research Institute, Nashville, TN, USA. 25 patients (1 ineligible) were treated.
Pre-assignment details
One enrolled patient had a disease-associated serious adverse event and died before starting treatment and was not included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| RRx-001: Dose Level 1 (10 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 6 |
| RRx-001: Dose Level 2 (16.7 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 3 |
| RRx-001: Dose Level 3 (24.6 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 3 |
| RRx-001: Dose Level 4 (33 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 4 |
| RRx-001: Dose Level 5 (55.0 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 3 |
| RRx-001: Dose Level 6 (83 mg/m2) Participants received RRx-001 by IV infusion every week for 2 Cycles. On completion, participants were offered further weekly doses, provided the Investigator and Medical Monitor agree it is warranted based on the status and symptomatology of their disease. | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | RRx-001: Dose Level 1 (10 mg/m2) | RRx-001: Dose Level 2 (16.7 mg/m2) | RRx-001: Dose Level 3 (24.6 mg/m2) | RRx-001: Dose Level 4 (33 mg/m2) | RRx-001: Dose Level 5 (55.0 mg/m2) | RRx-001: Dose Level 6 (83 mg/m2) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.15 years | 64.3 years | 67.1 years | 63.5 years | 59.5 years | 58.35 years | 61.3 years |
| ECOG Status ECOG 0 | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 6 Participants |
| ECOG Status ECOG 1 | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 18 Participants |
| ECOG Status ECOG 2 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 25 |
| serious Total, serious adverse events | 11 / 25 |
Outcome results
Primary
Number of Patients Who Had an Adverse Events
The total number of patients who experienced at least one adverse event while receiving treatment.
Time frame: From time of receiving a dose of RRx-001 through 92 days
Population: Total number of participants enrolled
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RRx-001: Dose Level 1 (10 mg/m2) to Dose Level 5 (83.0 mg/m2) | Number of Patients Who Had an Adverse Events | 25 Participants |