Gemcitabine and CT-011 for Resected Pancreatic Cancer
Study Details
Study Description
Brief Summary
Background:
-
In 2009, 49,096 patients were diagnosed with pancreatic cancer. Pancreatic cancer carries a poor prognosis with an overall 5-year relative survival rate of 5.6%.
-
Many doctors believe that individuals who have had surgery to remove pancreatic cancer should receive additional treatment, known as adjuvant therapy or adjuvant treatment, to prevent the cancer from returning. One chemotherapy drug that has been found to be effective in some patients with pancreatic cancer is called gemcitabine; it has been shown to improve patient survival by 6 months. Researchers are searching for new drugs or drug combinations to improve on these results.
-
One of the leading causes for immune suppression in cancer patients was suggested to be associated with the elevated expression of programmed cell death ligand 1 (PD-L1) human B7 homolog 1 (B7-H1) at tumor-involved sites, either by the tumor itself or by surrounding cells like regulatory immune cells, resulting in the local suppression and apoptosis of tumor infiltrating effector lymphocytes.
-
Some chemotherapy drugs kill cancer cells directly, but appear to prevent the immune system from helping in that fight. The experimental drug CT-011 is designed to help the immune system remain active to fight cancer cells. CT-011 has been tested in laboratories and studied for use with a number of other cancers, but it has not been given in combination with gemcitabine as a treatment for pancreatic cancer.
Objective:
- To test the safety and effectiveness of chemotherapy drugs gemcitabine and CT-011 as a follow-up treatment for pancreatic cancer that has been surgically removed.
Eligibility:
- Individuals at least 18 years of age who have had surgery to remove pancreatic cancer and have not had other types of follow-up treatments.
Design:
-
Participants will receive gemcitabine and CT-011 in 28-day cycles of treatment, and will be monitored throughout their treatment.
-
Participants who do not have serious side effects and remain cancer-free may receive this drug combination every 28 days for a total of 6 cycles.
-
Participants will have follow-up visits with additional blood tests every 2 months after stopping treatment for up to 2 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
RATIONALE:
-
CT-011 is a humanized immunoglobulin G 1 (IgG1) kappa recombinant monoclonal antibody against PD-1 receptor that blocks the interaction of PD-L1 with PD-1. CT-011 specifically binds to an epitope that is shared between the murine and the human PD-1 receptors on activated T cells, B cells, natural killer (NK) cells, and myeloid cells (CD14+ cells) and primarily functions in effector/memory T lymphocytes and in NK cells. In a functional bioassay, CT-011 was demonstrated to block the activity of PD-1 and to operate on CD4+CD45RO+ effector/memory T lymphocytes leading to attenuation of apoptotic processes.
-
CT-011 was studied in experimental murine tumor models of melanoma, lung cancer, fibrosarcoma, leukemia/lymphoma and colorectal carcinoma and was shown to inhibit tumor growth and extend the survival of tumor-bearing nude mice, and to generate tumor-specific protection against tumor re-challenge.
-
Recent findings have demonstrated that chemotherapies like paclitaxel, etoposide or fluorouracil (5-FU) induce the expression of the PD-L1 on tumor cell lines leading to an immune-suppressive environment and promoting PD-L1-mediated T cell apoptosis
The study will be conducted as an optimal two-stage phase II trial, in order to rule out an unacceptably low 50% of patients who do not receive the full dose of CT-011 (p0=0.50) in favor of a modestly high 80% fraction who receive the full dose of CT-011 (p1=0.80). It is anticipated that up to 32 patients may be enrolled onto this trial.
OBJECTIVES:
-
Primary endpoint: To determine the feasibility and safety of the combination of CT-011 and Gemcitabine in patients after primary macroscopic resection of pancreatic carcinoma.
-
Secondary endpoint: To determine if the addition of CT-011 to Gemcitabine can improve the median disease-free survival in resected pancreatic cancer.
DESIGN:
-
Eligible subjects will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies.
-
Participants will receive adjuvant combination CT-011 and Gemcitabine in 28-day cycles.
-
CT-011 will be given at a dose of 3mg/kg by intravenous infusion over 2 hours on day 1, one week prior to the first Gemcitabine infusion of each cycle.
-
Gemcitabine will be given at a dose of 1000mg/m^2 by intravenous infusion over 30 minutes on Days 8, 15 and 22 of each cycle.
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Treatment will be continued for a total of 6 cycles or until disease recurrence or grade IV non-hematological toxicity if occurred before the completion of 6 cycles.
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Participants will be monitored with frequent blood and urine tests throughout their treatment visits. Every other cycle (about every 2 months), participants will also have imaging studies to evaluate the experimental treatment.
-
Participants will have follow-up visits with additional blood tests every 2 months after stopping treatment for up to 2 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single arm Combination CT-011 and Gemcitabine |
Biological: CT-011
3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours.
Other Names:
Drug: Gemcitabine
1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Toxicity Evaluation: From Time of First Treatment With CT-011 (Pidilizumab, MDV9300) [2 years]
Patients presenting with symptoms possibly related to autoimmune reaction will be evaluated for organ specific autoimmune involvement, i.e: Acute abdominal symptoms should be evaluated for pancreatitis, including lipase and amylase levels; Persistent diarrhea should be evaluated for infection (c. diff). Any suspicion of colitis should be evaluated by a colonoscopy with biopsy. Visual symptoms should be immediately evaluated by an ophthalmologist. Generalized rash should be biopsied prior to local skin care, antihistamines or corticosteroids. Pulmonary symptoms will be evaluated immediately, including repeated PFTs (pulmonary function tests).
Secondary Outcome Measures
- Disease Response: Evaluated Using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (v1.1) [2 years]
Patients who have received at least one cycle of therapy will be evaluated for response every 8 weeks (every other cycle). Confirmatory scans will be obtained 4 weeks following initial documentation of objective or non-target disease response. Response will be evaluated on target and non-target lesions. The same method of assessment and same technique will be used to characterize each identified and reported lesion at baseline and during follow-up. Response will be reported as: Complete Response (CR); Disappearance of all target lesions Partial Response (PR); At least 30% decrease in the sum of the diameters of target lesions Progressive Disease (PD): At least 20% increase in the sum of the diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Eligibility Criteria
Criteria
-
Adult patients with histologic verification of carcinoma of the pancreas (T1-3, N0-1) who have undergone surgical resection within the past 4 - 12 weeks. Patients with R1 resections are excluded.
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Must meet all laboratory safety criteria and not have active or history of autoimmune disease or conditions, be treated with immunosuppressive drugs, or require the use of systemic steroids. Primary intraoperative chemotherapy will be allowed.
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Pregnant or nursing women will be excluded. Subjects with active infection, HIV, Hepatitis B or C will be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Georgia Regents University | Augusta | Georgia | United States | 30912 |
Sponsors and Collaborators
- Augusta University
Investigators
- Principal Investigator: Samir N. Khleif, MD, Augusta University
Study Documents (Full-Text)
None provided.More Information
Publications
- Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993 Jan;165(1):68-72; discussion 72-3.
- Miller RC, Iott MJ, Corsini MM. Review of adjuvant radiochemotherapy for resected pancreatic cancer and results from Mayo Clinic for the 5th JUCTS symposium. Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):364-8. doi: 10.1016/j.ijrobp.2008.11.069. Review.
- Saif MW. Adjuvant treatment of pancreatic cancer in 2009: where are we? Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009. JOP. 2009 Jul 6;10(4):373-7. Review.
- Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg. 1999 Jul;189(1):1-7.
- 11-C-0100
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | Combination CT-011 and Gemcitabine CT-011: 3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. Gemcitabine: 1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. |
| Period Title: Overall Study | |
| STARTED | 2 |
| COMPLETED | 2 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | Combination CT-011 and Gemcitabine CT-011: 3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. Gemcitabine: 1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. |
| Overall Participants | 2 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
2
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
2
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
2
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
2
100%
|
Outcome Measures
| Title | Toxicity Evaluation: From Time of First Treatment With CT-011 (Pidilizumab, MDV9300) |
|---|---|
| Description | Patients presenting with symptoms possibly related to autoimmune reaction will be evaluated for organ specific autoimmune involvement, i.e: Acute abdominal symptoms should be evaluated for pancreatitis, including lipase and amylase levels; Persistent diarrhea should be evaluated for infection (c. diff). Any suspicion of colitis should be evaluated by a colonoscopy with biopsy. Visual symptoms should be immediately evaluated by an ophthalmologist. Generalized rash should be biopsied prior to local skin care, antihistamines or corticosteroids. Pulmonary symptoms will be evaluated immediately, including repeated PFTs (pulmonary function tests). |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study discontinued due to drug supply issues prior to analysis; no meaningful data derived. |
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | Combination CT-011 and Gemcitabine CT-011: 3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. Gemcitabine: 1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. |
| Measure Participants | 0 |
| Title | Disease Response: Evaluated Using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (v1.1) |
|---|---|
| Description | Patients who have received at least one cycle of therapy will be evaluated for response every 8 weeks (every other cycle). Confirmatory scans will be obtained 4 weeks following initial documentation of objective or non-target disease response. Response will be evaluated on target and non-target lesions. The same method of assessment and same technique will be used to characterize each identified and reported lesion at baseline and during follow-up. Response will be reported as: Complete Response (CR); Disappearance of all target lesions Partial Response (PR); At least 30% decrease in the sum of the diameters of target lesions Progressive Disease (PD): At least 20% increase in the sum of the diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study discontinued due to drug supply issues prior to analysis; no meaningful data derived. |
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | Combination CT-011 and Gemcitabine CT-011: 3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. Gemcitabine: 1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Single Arm | |
| Arm/Group Description | Combination CT-011 and Gemcitabine CT-011: 3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. Gemcitabine: 1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. | |
All Cause Mortality |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Dr. Samir Khleif |
|---|---|
| Organization | Georgetown University |
| Phone | (202) 687-0100 |
| snk48@georgetown.edu |
- 11-C-0100