A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)
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| ClinicalTrials.gov Identifier: NCT01124786 |
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Recruitment Status :
Completed
First Posted : May 17, 2010
Results First Posted : April 17, 2014
Last Update Posted : April 17, 2014
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Pancreatic Adenocarcinoma | Drug: CO-1.01 Drug: Gemcitabine | Phase 2 |
Pancreatic cancer is a very serious form of cancer. The majority of patients present with unresectable disease, and the condition is often not diagnosed until the cancer is relatively advanced. The standard first-line treatment for patients with unresectable pancreatic cancer is gemcitabine monotherapy. Unfortunately many of these patients fail to derive benefit from this treatment. No clinical or molecular marker has been established to predict benefit from gemcitabine therapy, so patients are treated empirically until evidence of disease progression or worsening performance status.
The potential for human equilibrative nucleoside transporter-1 (hENT1) expression to predict survival in gemcitabine-treated patients has been studied, and data suggest that patients with low levels of tumor cell hENT1 expression derive less benefit from gemcitabine treatment than patients with high levels of tumor cell hENT1 expression. These data support the hypothesis to be tested in this study that patients with pancreatic tumors expressing low levels of hENT1 will derive minimal benefit from gemcitabine, but will receive benefit from CO-1.01 (gemcitabine elaidate) which enters tumor cells in a hENT1-independent fashion.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 367 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Randomized, Open-Label, Multicenter Study Comparing CO-1.01 With Gemcitabine as First-Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma |
| Study Start Date : | May 2010 |
| Actual Primary Completion Date : | November 2012 |
| Actual Study Completion Date : | June 2013 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: CO-1.01 |
Drug: CO-1.01
1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks |
| Active Comparator: gemcitabine |
Drug: Gemcitabine
1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks |
- Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression [ Time Frame: Monthly follow up after treatment discontinuation until death, up to 1.5 years. ]
- Overall Survival in All Patients and Patients With hENT1 Expression [ Time Frame: Monthly follow up after treatment discontinuation until death, up to 1.5 years ]
- ORR, Duration of Response, and Progression Free Survival (PFS) in Patients With Measurable/Evaluable Disease, Using RECIST 1.1, up to 1.5 Years [ Time Frame: Every 8 weeks ]
- Cancer Antigen (CA)19-9 Response Rates [ Time Frame: Every 4 weeks, up to 1.5 years ]
- Drug Tolerability and Toxicity [ Time Frame: Every week, up to 1.5 years ]
- Change From Baseline in Pain Severity [ Time Frame: Every 4 weeks, up to 1.5 years ]
- Change From Baseline in Health Status [ Time Frame: Every 4 weeks, up to 1.5 years ]
- Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling [ Time Frame: 30 days after first dose ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Metastatic pancreatic ductal adenocarcinoma (i.e., Stage 4).
- Histological/cytological confirmation of metastatic tissue (not primary tumor) by a central pathology laboratory (H&E stain) to ensure sufficient material is available for later hENT1 analysis.
- Adjuvant chemotherapy/radiotherapy ≥ 6 months prior to randomization.
- Palliative radiotherapy (if administered) ≥ 1 month prior to randomization.
- CT scan ≤30 days prior to randomization
- Performance Status (ECOG) 0 or 1.
- Estimated life expectancy ≥ 12 weeks.
- Age ≥ 18 years.
- Adequate hematological and biological function.
- Written consent on an Institutional Review Board/Institutional Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.
Exclusion Criteria:
- Prior palliative chemotherapy for pancreatic cancer.
- Radical pancreatic resections (e.g., Whipple procedure) are not allowed < 6 months prior to randomization. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures (e.g., stents) are not allowed < 14 days prior to randomization. In both cases the patient must be sufficiently recovered and stable.
- Symptomatic brain metastases.
- Participation in other investigational drug clinical studies ≤ 30 days prior to randomization.
- Concomitant treatment with prohibited medications.
- History of allergy to gemcitabine or eggs.
- Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
- Any disorder that would hamper protocol compliance.
- Prior nonpancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery or radiotherapy alone must be in remission ≥ 3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.
- Females who are pregnant or breastfeeding.
- Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last study treatment). Adequate forms of contraception are double-barrier methods (condoms or diaphragm with spermicidal jelly or foam); oral, depot, or injectable contraceptives; intrauterine devices; tubal ligation.
- Any other reason the investigator considers the patient should not participate in the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01124786
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| Responsible Party: | Clovis Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT01124786 |
| Other Study ID Numbers: |
CO-101-001 |
| First Posted: | May 17, 2010 Key Record Dates |
| Results First Posted: | April 17, 2014 |
| Last Update Posted: | April 17, 2014 |
| Last Verified: | March 2014 |
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cancer metastatic pancreatic pancreas adenocarcinoma gemcitabine |
human equilibrative nucleoside transporter-1 (hENT1) CO-1.01 CO-101 CO101 Stage 4 Stage IV |
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
Gemcitabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |