Locally Advanced Malignant NeoplasmPhase 1CRITNCT01903083
Chemoimmunotherapy and Radiation in Pancreatic Cancer
A Phase 1 study testing Tadalafil, Gemcitabine and Radiation in people with Locally Advanced Malignant Neoplasm, run by Providence Health & Services at 1 site in United States.
Trial summary
The goal of this study is to evaluate the safety of combination treatment that includes chemotherapy, radiation therapy, and immunotherapy in patients with pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Malignant Neoplasm
- What is being tested?
- Tadalafil, Gemcitabine and Radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- Pancreatic adenocarcinoma
- Locally advanced unresectable disease, or borderline resectable disease
- ECOG (Eastern Cooperative Oncology Group)Performance Status 0 or 1
- Ability to provide consent and comply with study protocol
- Women of child-bearing potential must have a negative pregnancy test and avoid pregnancy during the study
Who cannot join
- Age < 18
- History of other malignancy in previous 2 years except carcinoma in situ of the cervix or bladder, or non-melanoma skin cancer
- Previous chemotherapy or radiation therapy for pancreatic cancer or previous radiation to the target field
- Clinically active autoimmune disease or active infection
- History of heart attack within 90 days or stroke within 6 months, hypertension requiring change in blood pressure medications in the last 4 weeks, hypotension, uncontrolled arrhythmias, heart failure (NYHA >= Class 2 in last 6 months), unstable angina, or angina during sexual activity
- Use of nitrates or nitroglycerin
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- History of hereditary degenerative retinal disorders including retinitis pigmentosa
- Chronic systemic corticosteroid use at supra-physiologic doses
- Use of recreational drugs called 'poppers' like amyl nitrite and butyl nitrite
- Blood test results (neutrophils < 1000 /uL (microliter); hemoglobin < 9 gm /dL; platelet count < 1000 cells / uL; significant coagulopathy; significant liver or renal dysfunction
Trial locations and contacts
1 site in 1 country.
United States1 site
Portland Providence Medical Center
Portland, Oregon, 97213
About this study
Official title: Phase I Trial of Chemoimmunotherapy and Hypofractionated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.
The goal of this study is to evaluate the safety of combination treatment that includes chemotherapy, radiation therapy, and immunotherapy in patients with pancreatic cancer.
Read the detailed description
This study is for borderline resectable and advanced pancreatic cancer patients. Patients will receive chemotherapy with gemcitabine and immunotherapy with daily tadalafil during the first 21 days of treatment. On study day 22, patients will receive the first of three planned doses of radiation therapy and continue daily tadalafil. Patients are then evaluated to determine if they are candidates for pancreaticoduodenectomy. Patients who are not candidates will continue daily tadalafil and receive gemcitabine chemotherapy. Patients who have surgery will resume daily tadalafil and gemcitabine chemotherapy following recovery from surgery. Patients will receive up to four cycles of gemcitabine.
- Conditions
- Locally Advanced Malignant Neoplasm
- Being tested
- Tadalafil, Gemcitabine, Radiation, Pancreaticoduodenectomy
- Keywords
- Pancreas, Pancreatic cancer, Immunotherapy, Chemotherapy, Radiation, Surgery, Pancreaticoduodenectomy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Cialis
One 2.5 mg tablet is self-administered orally by the study participant on a once daily basis.
GemcitabineDrug
Also called Gemzar
Three doses of gemcitabine (1000 mg / m^2)are given over a 21-day cycle. Patients may receive up to 4 cycles.
RadiationRadiation
Patients will receive 3 doses of radiation (8-10 Gy per fraction).
PancreaticoduodenectomyProcedure or surgery
Surgical resection.
| Study group | Role | What they receive |
|---|---|---|
| Immunochemoradiotherapy | Experimental | Immunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients. Receives: Drug: Tadalafil; Drug: Gemcitabine; Radiation: Radiation; Procedure: Pancreaticoduodenectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Patients will return be seen in the clinic 8 times over the first 50 days for an evaluation of adverse events and toxicities before being evaluated for surgery. Patients who are not candidates for surgery will be seen in clinic 10 more times over the next 85 days for safety evaluations, and patients who have surgery will be seen 10 times over the 85 days following recovery from surgery for safety evaluations.
Measured: 135 Days
Secondary outcomes (2)
Immune Infiltration in pancreaticoduodenectomy tissue
For surgery patients, formalin fixed and paraffin-embedded tumor tissue obtained during surgery will be sectioned and immunohistology performed to determine the tumor inflammatory micro-environment and the degree of macrophage and T cell inflammation.
Measured: 50 Days
Quantification of T cells in peripheral blood pre- and post-treatment
Patients will provide a pre-treatment blood sample and 4 blood samples over 135 days to evaluate the influence of the study treatment on immune parameters. For patients who have surgery, the time period will be longer depending on their recovery time. Post-treatment long term follow up will occur every 12 weeks (+/- 2 weeks) beyond post-recovery date (PRD) 85 for 6 visits. Blood will be collected for immune monitoring at each visit.
Measured: 135 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Malignant NeoplasmStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Todd Crocenzi, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01903083
- Sponsor's protocol ID
- 13-026A
- Acronym
- CRIT
- Status last verified
- Jan 2018
- First submitted
- 2 Jul 2013
- Last updated
- 1 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, Jutric Z, Young K, Bahjat KS, Gough MJ, Crittenden MR. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016.
PubMed 27532020
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Chemoimmunotherapy and Hypofractionated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.
- ClinicalTrials.gov ID
- NCT01903083
- Acronym / sponsor ID
- CRIT / 13-026A
- Conditions
- Locally Advanced Malignant Neoplasm
- Keywords
- Pancreas, Pancreatic cancer, Immunotherapy, Chemotherapy, Radiation, Surgery, Pancreaticoduodenectomy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- Jul 2013
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 19 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to evaluate the safety of combination treatment that includes chemotherapy, radiation therapy, and immunotherapy in patients with pancreatic cancer.
Detailed description
This study is for borderline resectable and advanced pancreatic cancer patients. Patients will receive chemotherapy with gemcitabine and immunotherapy with daily tadalafil during the first 21 days of treatment. On study day 22, patients will receive the first of three planned doses of radiation therapy and continue daily tadalafil. Patients are then evaluated to determine if they are candidates for pancreaticoduodenectomy. Patients who are not candidates will continue daily tadalafil and receive gemcitabine chemotherapy. Patients who have surgery will resume daily tadalafil and gemcitabine chemotherapy following recovery from surgery. Patients will receive up to four cycles of gemcitabine.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immunochemoradiotherapy | Experimental | Drug: Tadalafil, Drug: Gemcitabine, Radiation: Radiation, Procedure: PancreaticoduodenectomyImmunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Pancreatic adenocarcinoma
- Locally advanced unresectable disease, or borderline resectable disease
- ECOG (Eastern Cooperative Oncology Group)Performance Status 0 or 1
- Ability to provide consent and comply with study protocol
- Women of child-bearing potential must have a negative pregnancy test and avoid pregnancy during the study
Key exclusion criteria (10 listed)
- Age < 18
- History of other malignancy in previous 2 years except carcinoma in situ of the cervix or bladder, or non-melanoma skin cancer
- Previous chemotherapy or radiation therapy for pancreatic cancer or previous radiation to the target field
- Clinically active autoimmune disease or active infection
- History of heart attack within 90 days or stroke within 6 months, hypertension requiring change in blood pressure medications in the last 4 weeks, hypotension, uncontrolled arrhythmias, heart failure (NYHA >= Class 2 in last 6 months), unstable angina, or angina during sexual activity
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 |
|---|---|---|
| TadalafilAlso: CialisOne 2.5 mg tablet is self-administered orally by the study participant on a once daily basis. | Drug | Immunochemoradiotherapy |
| GemcitabineAlso: GemzarThree doses of gemcitabine (1000 mg / m^2)are given over a 21-day cycle. Patients may receive up to 4 cycles. | Drug | Immunochemoradiotherapy |
| RadiationPatients will receive 3 doses of radiation (8-10 Gy per fraction). | Radiation | Immunochemoradiotherapy |
| PancreaticoduodenectomySurgical resection. | Procedure or surgery | Immunochemoradiotherapy |
Primary outcome
Safety
Time frame: 135 Days
Patients will return be seen in the clinic 8 times over the first 50 days for an evaluation of adverse events and toxicities before being evaluated for surgery. Patients who are not candidates for surgery will be seen in clinic 10 more times over the next 85 days for safety evaluations, and patients who have surgery will be seen 10 times over the 85 days following recovery from surgery for safety evaluations.
2 secondary outcomes
Immune Infiltration in pancreaticoduodenectomy tissue
Time frame: 50 Days
Quantification of T cells in peripheral blood pre- and post-treatment
Time frame: 135 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2018.
- Derived from this study: PubMed 27532020Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, Jutric Z, Young K, Bahjat KS, Gough MJ, Crittenden MR. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016.
- Individual participant dataSharing planned: No
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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.
Todd Crocenzi, MD principal investigator
Providence Health & Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tadalafil, Gemcitabine and Radiation in people with Locally Advanced Malignant Neoplasm, run by Providence Health & Services 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?
The sponsor lists 5 inclusion and 10 exclusion criteria. 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: finished, as of the sponsor's last update on 1 Feb 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety (time frame: 135 Days). 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 NCT01903083, which also lists 1 linked publication.
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 1 Feb 2018.