Metastatic Pancreatic Adenocarcinoma
Conditions
Keywords
cancer, metastatic, pancreatic, pancreas, adenocarcinoma, gemcitabine, human equilibrative nucleoside transporter-1 (hENT1), CO-1.01, CO-101, CO101, Stage 4, Stage IV, Gemcitabine-Refractory, Second-Line Therapy
Brief summary
The purpose of this study is to determine whether CO-1.01 is safe and effective for treating metastatic pancreatic cancer that did not respond to gemcitabine.
Detailed description
Pancreatic tumors with low hENT1 expression may show less benefit from gemcitabine compared with those with higher expression of this nucleoside transporter. Nonclinical studies indicate that CO-1.01, a gemcitabine derivative, is effective independent of such transporters. Thus patients with low or no meaningful expression of hENT1 who failed to respond to gemcitabine might derive benefit from CO1.01 before needing alternative (combination) chemotherapy. Furthermore, the PK profiles of CO-1.01 and gemcitabine are dissimilar and this may confer additional clinical benefit on CO1.01.
Interventions
DRUGCO-1.01
1250 mg/m2/day administered on Days 1, 8, and 15 in 4-week treatment cycles. Patients who have SD or better at the Week 8 assessment and who adequately tolerated the first 2 cycles of treatment may continue CO-1.01 at the same or an increased dose (1400 mg/m2) for Cycle 3 and subsequent cycles.
Sponsors
Clovis Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Gemcitabine-refractory metastatic ductal adenocarcinoma of the pancreas * At least 1 measurable lesion according to RECIST 1.1 criteria * Computerized tomography (CT) scan ≤ 28 days prior to CO-1.01 * First-line treatment included at least 3 doses of gemcitabine (as monotherapy or combination therapy) with the last dose administered at least 2 weeks prior to CO 1.01 * Radiological best response of disease progression after 1st-line treatment (no radiological stable disease or better allowed at any time) * Patients who experienced progressive disease during (neo)-adjuvant gemcitabine-based therapy are also eligible * Patients who have completed previous adjuvant therapy without progression, then subsequently have a radiological best response of disease progression on 1st line gemcitabine for metastatic disease are eligible 2. No hENT1 expression in primary or metastatic tumor sample, confirmed with IHC by a core pathology laboratory prior to study entry also eligible 3. Performance Status (ECOG) 0 or 1 4. Age ≥18 years 5. Palliative radiotherapy (if administered) ≥2 weeks prior to CO-1.01 6. Adequate hematological and biological function, with no residual gemcitabine-related toxicity 7. Written consent on an Institutional Review Board (IRB)-approved IC Form prior to any study-specific evaluation
Exclusion criteria
1. Patients who have had stable disease, partial response or complete response to first line gemcitabine-based therapy 2. First-line chemotherapy regimen that does not contain gemcitabine 3. First-line treatment discontinued due to intolerable gemcitabine-induced toxicity 4. Second or subsequent line therapy for advanced disease. Prior exposure to CO-1.01 or prior randomization in a protocol studying CO-1.01 (e.g.,Protocol CO-101-001) 5. Tumor that cannot be evaluated for hENT1 expression or that has hENT1 staining in \>50% of cells 6. Symptomatic brain metastases 7. Concomitant treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment \[except corticosteroids and megestrol acetate\], or immunotherapy) ≤14 days prior to CO-1.01 8. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures are not allowed \<14 days prior to CO-1.01 administration; stenting procedures are permissible at any time prior to dosing; in all cases, the patient must be sufficiently recovered and stable 9. History of allergy to gemcitabine or eggs 10. Females who are pregnant or breastfeeding 11. Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last dose of CO-1.01) 12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including active infection, arterial thrombosis, or symptomatic pulmonary embolism) 13. Any other reason for which the investigator considers the patient should not participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease Control Rate (CR, PR, or SD) using RECIST 1.1 | Every 8 weeks until disease progression |
Secondary
| Measure | Time frame |
|---|---|
| CA 19-9 response rate | Every 4 weeks |
| Progression-free survival (PFS) | Every 8 weeks |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Every week |
| Overall Response Rate (ORR) | Every 8 weeks |
| Median progression-free survival | 3, 6, 9, and 12 months |
| Median overall survival | 3, 6, 9, and 12 months |
| Duration of response | Every 8 weeks |
| Overall survival (OS) | 3, 6, 9, and 12 months |
Countries
United States
Outcome results
None listed