Not provided
Not provided
Not provided
Not provided
Not provided
The study placed on temporarily hold to enrollment due to quality testing necessary for the study drug.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a study of ARQ-761 (beta-lapachone) with gemcitabine/nab-paclitaxel chemotherapy in subjects with advanced (metastatic, unresectable, or recurrent) pancreatic cancer that has not been treated with gemcitabine.
Screening:
This visit may last approximately 1-2 hours. Visits that included radiologic evaluation may last longer, approximately 2-3 hours.
The treatment consists of:
A 2 week lead-in monotherapy of ARQ-761 - they will receive the current dose of ARQ761 alone
o The amount of ARQ-761 that will be given to you will depend on the time at which you are enrolled in the study.
Afterwards the 28-day cycle of combination treatment of ARQ-761 along with gemcitabine (1000 mg/m2) + nab-paclitaxel (125 mg/m2) will begin
Lead-in 2 weeks before the combination therapy begins:
Monotherapy of ARQ-761
Day 1:
Combination Therapy:
Cycle 1 Day 1
Combination Treatment regimen:
After waiting for 60 minutes (1 hour) then:
ARQ 761 administered via intravenous (IV) over 120 minutes (2 hours)
Biopsy of their tumor
PKs (pharmacokinetics) (consist of drawing of approximately ½ teaspoon of blood to determine what their body does to the study drug) will be collected at:
PDs (pharmacodynamics) (consist of drawing of approximately ½ teaspoon of blood to examine the response of protein biomarkers in patients treated with ARQ-761during the clinical trial) will be collected:
Clinic Visit: 8 Hours
Cycle 1 Day 8
Clinic Visit: 2 hours
Cycle 1 Day 15
Treatment regimen:
After waiting for 60 minutes (1 hour) then:
ARQ 761 administered via intravenous (IV) over 120 minutes (2 hours)
PKs (pharmacokinetics) (consist of drawing of approximately ½ teaspoon of blood to determine what their body does to the study drug) will be collected at:
PDs (pharmacodynamics) (consist of drawing of approximately ½ teaspoon of blood to examine the response of protein biomarkers in patients treated with ARQ-761during the clinical trial) will be collected:
Clinic Visit: 8 hours
Cycle 2 Day 1
Combination treatment regimen same as for Cycle 1 Day 1
Clinic Visit: 5 - 6 hours
Cycle 2 Day 8
Clinic Visit: 2-3 hours
Cycle 2 Day 15
Combination treatment regimen same as for Cycle 1 Day 1
Clinic Visit: 5 - 6 hours
Cycle 2 Day 27
• CT scan of their chest/abdomen/pelvis
Clinic Visit: 1 - 2 hours
Cycle 3 and all subsequent odd cycles Day 1
Combination treatment regimen same as for Cycle 1 Day 1
Clinic Visit: 5 - 6 hours
Cycle 3 and all subsequent odd cycles Day 8
Clinic Visit: 2-3 hours
Cycle 3 and all subsequent odd cycles Day 15
Clinic Visit: 6 hours
Cycle 4 and all subsequent even cycles Day 1
Combination treatment regimen same as for Cycle 1 Day 1
Clinic Visit: 6 hours
Cycle 4 and all subsequent even cycles Day 8
Clinic Visit: 2-3 hours
Cycle 4 and all subsequent even cycles Day 15
Combination treatment regimen same as for Cycle 1 Day 1
Clinic Visit: 6 hours
Cycle 4 and all subsequent even cycles Day 27
• CT scan of their chest/abdomen/pelvis
Clinic Visit: 1 - 2 hours
Off-Treatment Visit/End of Study Visit
Clinic Visit: 1 - 2 hours
Follow-up Procedures
They will be seen once at 4 weeks after completion of (or early withdrawal from) study treatment. This visit will be repeated every 4 weeks until resolution of any side effects. The following will be done at this visit:
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARQ-761 | Experimental | A 2 week lead-in monotherapy of ARQ-761 (The amount of ARQ-761 that will be given to the participant will depend on the time at which the participant was enrolled in the study Afterwards the 28-day cycle of combination treatment of ARQ-761 along with gemcitabine (1000 mg/m2) + nab-paclitaxel (125 mg/m2) will begin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARQ-761 | Drug | Dose Level 1: ARQ761 195 mg IV D1, D15 Gemcitabine 1000 mg/m2 D1, 8, 15 Nab paclitaxel 125 mg/m2 D1, 8, 15 Dose Level 2: ARQ761 290 mg IV D1, D15 Gemcitabine 1000 mg/m2 D1,8,15 Dose Level 3: ARQ761 390 mg IV D1, D15 Gemcitabine 1000 mg/m2 D1,8,15 Nab-paclitaxel 125 mg/m2 D1,8,15 Expansion Dose Level: ARQ761 390 IV mg or as tolerated D1, 15 Gemcitabine 1000 mg/m2 D1,8,15 Nab-Paclitaxel 125 mg/m2 D1,8,15 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose | Determine the maximum tolerated dose (MTD) of ARQ761 when given in combination with gemcitabine and nab-paclitaxel (GEM-Nab-Pac). | Day 8, Day 1 and Day 15 every 28 days for 168 days or until disease progression, Off Treatment (Up to 8 months) , and 4 weeks after treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety will be assessed by quantifying toxicities using the NCI's CTCAE v4.0 toxicity criteria | Safety will be assessed by quantifying toxicities using the NCI's CTCAE v4.0 toxicity criteria. | Day 8 , Day 1 and Day 15 every 28 days for 168 days or until disease progression, Off Treatment (Up to 8 months) , and 4 weeks after treatment. |
Not provided
Inclusion Criteria:
Subjects must have a histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic, unresectable, or recurrent.
Has received at most 1 line of prior non-gemcitabine chemotherapy for:
Prior and concurrent therapy4. Measurable disease is required per RECIST criteria 1.1.
5. Age ≥18 years. 6. ECOG performance status 0 or 1 7. Anticipated life expectancy ≥ three months. 8. Central venous access 9. Availability of unstained slides or paraffin block tissue from archived tumor specimen. If not available the subject will undergo a fresh biopsy.
10. Specific pretreatment clinical laboratory parameters that are required within 14 days prior to registration.
11. Subjects must be recovered from any toxicity related to prior anti-neoplastic therapy (to grade <1).
12. Women of child-bearing potential and men 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.
Exclusion Criteria:
8. Any condition that confounds the ability to interpret data from the study. 9. Unwillingness or inability to comply with study procedures.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Muhammad Beg, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21231 | United States | ||
Not provided
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C014638 | beta-lapachone |
| D000093542 | Gemcitabine |
| C520255 | 130-nm albumin-bound paclitaxel |
| D000068196 | Albumin-Bound Paclitaxel |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Gemcitabine | Drug | Therapy after lead in Phase: You will receive Gemcitabine (1000mg/m2) administered intravenously on Days 1,8, 15-every 28 days. All cycles are 28 days in duration and there are no rest periods between cycles. You may continue treatment after cycle 6 until disease progression. |
|
|
| nab-paclitaxel | Drug | Therapy after lead in phase: You will receive nab-paclitaxel (125 mg/m2) administered intravenously on Days 1,8, 15-every 28 days. All cycles are 28 days in duration and there are no rest periods between cycles. You may continue treatment after cycle 6 until disease progression. |
|
|
| Overall Response Rate |
CT Chest/Abdomen/Pelvis to determine clinical activity as defined by overall response rate (ORR). |
| Imaging will be done every 2-3 months until you are off treatment (Up to 8 months). |
| Progression Free Survival | CT Chest/Abdomen/Pelvis to determine clinical activity as defined by Progression Free Survival . | Imaging will be done every 2nd cycle starting with week 10 (cycle 2) until you are off treatment (Up to 8 months). |
| Time To Progression | CT Chest/Abdomen/Pelvis to determine clinical activity as defined by Time To Progression. | Imaging will be done every 2nd cycle starting with week 10 (cycle 2) until you are off treatment (Up to 8 months). |
| Pharmacokinetic Profile | The pharmacokinetic profile of ARQ761 will be determined by measurement of blood levels at predetermined time points. | During Cycle 1 Day 1 and Cycle 1 Day 15 |
| Tolerability | Tolerability will be assessed by quantifying toxicities using the NCI's CTCAE v4.0 toxicity criteria. | Day 8, Day 1 and Day 15 every 28 days for 168 days or until disease progression, Off Treatment (Up to 8 months) , and 4 weeks after treatment. |
| UT Southwestern Medical Center |
| Dallas |
| Texas |
| 75390-8852 |
| United States |
| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |