Study to Evaluate Efficacy of CO-1.01 as Second Line Therapy for Gemcitabine-Refractory Stage IV Pancreatic Adenocarcinoma

Metastatic Pancreatic Adenocarcinoma Clinical Trial

Official title:

A Phase II, Open-Label, Multicenter Study to Evaluate the Antitumor Efficacy of CO-1.01 for Infusion as Second-Line Therapy for Gemcitabine- Refractory Patients With Stage IV Pancreatic Adenocarcinoma and No Tumor hENT1 Expression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01233375
• Other study ID #: CO-101-003
• Status: Completed
• Phase: Phase 2
• Start date: April 2011
• Est. completion date: March 2013

Study information

• Verified date: March 2019
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

Drug:
• CO-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.

Locations

Country	Name	City	State
United States	Piedmont Healthcare Research Institute (PHRI)	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	Palm Beach Institute / Collaborative Research Group	Boynton Beach	Florida
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Norton Cancer Institute Research Program	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center, Milstein Hospital	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Arizona Cancer Center at University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (CR, PR, or SD) using RECIST 1.1		Every 8 weeks until disease progression
Secondary	Overall Response Rate (ORR)		Every 8 weeks
Secondary	CA 19-9 response rate		Every 4 weeks
Secondary	Progression-free survival (PFS)		Every 8 weeks
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		Every week
Secondary	Overall survival (OS)		3, 6, 9, and 12 months
Secondary	Median progression-free survival		3, 6, 9, and 12 months
Secondary	Median overall survival		3, 6, 9, and 12 months
Secondary	Duration of response		Every 8 weeks