Pancreatic NeoplasmsPhase 2NCT01313416
Gemcitabine and CT-011 for Resected Pancreatic Cancer
A Phase 2 study testing CT-011 and Gemcitabine in people with Pancreatic Neoplasms and Cancer of the Pancreas, run by Augusta University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neoplasms, Cancer of the Pancreas, Neoplasms Pancreatic
- What is being tested?
- CT-011 and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Jan 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
- 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.
- 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.
- Pregnant or nursing women will be excluded. Subjects with active infection, HIV, Hepatitis B or C will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study to Test the Feasibility of the Combination of Gemcitabine and Anti-PD1 Monoclonal Antibody (CT-011) in the Treatment of Resected Pancreatic Cancer
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.
Read more
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.
Read the 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.
- 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.
- 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.
- Conditions
- Pancreatic Neoplasms, Cancer of the Pancreas, Neoplasms Pancreatic, Pancreatic Cancer, Pancreas Cancer
- Being tested
- CT-011, Gemcitabine
- Keywords
- Adjuvant Therapy, Recombinant Monoclonal Antibody, Adenocarcinoma of the Pancreas, Vaccination, PD-1 Receptor, Pancreas Cancer, Pancreatic Cancer
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT-011Biological
Also called Anti-PD1 Antibody
3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours.
GemcitabineDrug
Also called Gemzar
1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Combination CT-011 and Gemcitabine Receives: Biological: CT-011; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity Evaluation: From Time of First Treatment With CT-011 (Pidilizumab, MDV9300)
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).
Measured: 2 years
Secondary outcomes (1)
Disease Response: Evaluated Using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (v1.1)
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2011 (estimated)
- Study startSep 2012
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: Drug supply issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pancreatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samir N. Khleif, Augusta University
- Investigators
- Samir N. Khleif, MD, Principal investigator, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313416
- Sponsor's protocol ID
- 11-C-0100
- Status last verified
- Jun 2019
- First submitted
- 10 Mar 2011
- Last updated
- 10 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Comprehensive data will be reported, not individual participant data.
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. doi: 10.1016/s0002-9610(05)80406-4.
PubMed 8380315Sener 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. doi: 10.1016/s1072-7515(99)00075-7.
PubMed 10401733Saif 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.
PubMed 19581737Miller 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.
PubMed 19735864
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Test the Feasibility of the Combination of Gemcitabine and Anti-PD1 Monoclonal Antibody (CT-011) in the Treatment of Resected Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01313416
- Acronym / sponsor ID
- 11-C-0100
- Conditions
- Pancreatic Neoplasms, Cancer of the Pancreas, Neoplasms Pancreatic, Pancreatic Cancer, Pancreas Cancer
- Keywords
- Adjuvant Therapy, Recombinant Monoclonal Antibody, Adenocarcinoma of the Pancreas, Vaccination, PD-1 Receptor, Pancreas Cancer, Pancreatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug supply issues
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Study start
- Sep 2012 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 11 Mar 2011 (estimated)
- Results
- Posted 10 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
- 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.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Biological: CT-011, Drug: GemcitabineCombination CT-011 and Gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CT-011Also: Anti-PD1 Antibody3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. | Biological | Single arm |
| GemcitabineAlso: Gemzar1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle. | Drug | Single arm |
Primary outcome
Toxicity Evaluation: From Time of First Treatment With CT-011 (Pidilizumab, MDV9300)
Time frame: 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).
1 secondary outcome
Disease Response: Evaluated Using the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (v1.1)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8380315Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993 Jan;165(1):68-72; discussion 72-3. doi: 10.1016/s0002-9610(05)80406-4.
- Background: PubMed 10401733Sener 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. doi: 10.1016/s1072-7515(99)00075-7.
- Background: PubMed 19581737Saif 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.
- Background: PubMed 19735864Miller 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.
- Individual participant dataSharing planned: No. Comprehensive data will be reported, not individual participant data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samir N. Khleif, MD principal investigator
Augusta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CT-011 and Gemcitabine in people with Pancreatic Neoplasms and Cancer of the Pancreas, run by Augusta University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity Evaluation: From Time of First Treatment With CT-011 (Pidilizumab, MDV9300) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01313416, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2019.