Pancreatic CancerPhase 1NCT02154737
Gemcitabine and Pulse Dose Erlotinib in Second Line Treatment of Advanced Pancreatic Cancer
A Phase 1 study testing Gemcitabine and Erlotinib in people with Pancreatic Cancer, run by Tony Reid, M.D., Ph.D. at 1 site in United States.
Trial summary
The purpose of this study is to see whether an altered schedule of giving erlotinib in combination with gemcitabine will be safe and might improve the results of the treatment for advanced cancer of the pancreas. Gemcitabine and erlotinib are commercially available. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Gemcitabine and Erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to 3 Sep 2020
- 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
- Pathologically confirmed advanced pancreatic cancer defined as non-operable in a curative intent, locally recurrent, or metastatic disease.
- Measureable disease by (Response Evaluation Criteria in Solid Tumors) RECIST v1.1. Measureable lesions will be confirmed by radiological imaging.
- Progressive disease by (Response Evaluation Criteria in Solid Tumors) RECIST criteria during or after treatment with first-line chemotherapy (disease free interval must be less than 6 months) and have not received further second-line chemotherapy. Patients treated with prior chemo-radiation to the primary pancreatic tumor, for which the chemotherapeutic agent was used as a radio-sensitizing agent, are eligible.
- Age >18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0-2.
- Life expectancy of >2 months.
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- Adequate laboratory parameters: All tests to be performed within 5 days prior to the first dose of erlotinib
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
- Women of child bearing potential must have a negative pregnancy test at screening.
Who cannot join
- Radiation within 4 weeks of study enrollment. Radiotherapy not permitted while on study. Exception: palliative radiotherapy of metastasis in extremities is allowed, but such lesions cannot be used as target or non-target lesions.
- Investigational compound within 4 weeks of enrollment or who are planning to receive other investigational drugs while participating in the study.
- Chemotherapy, biologics, immunotherapy, vaccine, cytokine therapy within 4 weeks prior to enrollment.
- Presence of untreated and/or symptomatic central nervous system (CNS) metastasis.
- Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, chronic renal disease, chronic pulmonary disease or active uncontrolled infection).
- Known diagnosis of human immunodeficiency virus (HIV) infection.
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- Presence of any other active or suspected acute or chronic uncontrolled infection or known symptomatic active hepatitis B or C.
- Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease.
- History of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer, cervical cancer in situ, localized biopsy-proven prostate cancer, or stage I colon cancer.
- Surgery within 3 weeks prior to enrollment.
- Patients taking Coumadin® or other agents containing warfarin, rivaroxaban, or dabigatran (exception: low dose Coumadin® (1 mg or less daily) administered prophylactically for maintenance of in-dwelling lines or ports is allowed).
- Patients taking any medications or substances that are inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A).
- Female patients who are pregnant or breast-feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: A Phase I, Open-label, Dose Escalation Study of Gemcitabine and Pulse Dose Erlotinib in Second Line Treatment of Advanced Pancreatic Cancer
The purpose of this study is to see whether an altered schedule of giving erlotinib in combination with gemcitabine will be safe and might improve the results of the treatment for advanced cancer of the pancreas.
Gemcitabine and erlotinib are commercially available. Gemcitabine is FDA approved as first-line treatment for patients with locally advanced, unresectable or metastatic cancer of the pancreas. Erlotinib is FDA approved in combination with gemcitabine for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
The FDA recommended dose for erlotinib is 100 mg daily. This study will investigate the experimental administration of higher doses of erlotinib given for only three days twice a month, a schedule called "pulse dosing".
Read the detailed description
Survival of pancreatic cancer patients remains poor, and treatment with erlotinib remains one of the few agents that have demonstrated increased survival. Alternative dosing schedules for erlotinib should be explored since chronic low dose therapy fails to achieve therapeutically effective concentrations for many patients and leads to increased skin toxicity and may induce acquired resistance without significantly impacting the tumor. Therefore, higher doses given for shorter periods of exposure, similar to the dosing of most chemotherapeutic agents, may achieve more effective therapeutic doses of than chronic low dose therapy and may minimize skin toxicity observed with erlotinib.
No phase I studies have been done with the combination of high dose pulse erlotinib therapy with gemcitabine. We propose a phase I dose escalation study of three day oral dosing of erlotinib with standard dose (1000 mg/m2) gemcitabine. The starting dose of erlotinib is 750 mg, approximately 50% of the the dose found to be safe in previous combination studies with carboplatin and paclitaxel and with pemetrexed [Riely et al. 2009, Davies et al. 2009]. Since acquired resistance can occur rapidly and 5 to 7 days of treatment is not better than 3 days of treatment, we will focus on a 3 day high-dose pulse treatment given every 14 days. This will provide 11 days between erlotinib dosing for the recovery of normal tissues. Levels of serum erlotinib will also be monitored due to considerable interpatient variability in the metabolism of erlotinib.
The hypotheses of this study are:
- High-dose pulse therapy with erlotinib can be safely administered with standard dose gemcitabine.
- High-dose pulse therapy with erlotinib will permit recovery of the epidermis between treatments resulting in reduced skin toxicity compared to chronic daily dosing.
- Disease control with high-dose pulse therapy may be superior to that with chronic low dose therapy.
- Conditions
- Pancreatic Cancer
- Being tested
- Gemcitabine, Erlotinib
- Keywords
- Pancreatic, Gemcitabine, Gemzar, erlotinib, Tarceva
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
Gemcitabine will be administered intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle.
ErlotinibDrug
Also called Tarceva
Erlotinib will be administered orally on Days 2-4 and Days 16-18 of a 28-day cycle in serial cohorts with doses of 750mg, 1000mg, 1250mg, 1500mg, 1750mg, and 2000mg.
| Study group | Role | What they receive |
|---|---|---|
| erlotinib and gemcitabine | Experimental | Erlotinib will be administered orally on Days 2-4 and Days 16-18 of a 28-day cycle in serial cohorts with doses of 750mg, 1000mg, 1250mg, 1500mg, 1750mg, and 2000mg
Gemcitabine will be administered intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Receives: Drug: Gemcitabine; Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities of each subject
Rate will be assessed through summaries of adverse events, clinical laboratory abnormalities, and changes in physical exam and vital signs. All subjects who receive a single dose of study medication will be considered evaluable for safety.
Measured: 28 days
Secondary outcomes (5)
Overall survival
the time from the first day of study treatment to date of death from any cause
Measured: 2 years
progression-free survival
the time from the first day of study treatment to date of disease progression
Measured: Up to 2 years
Best tumor response
a complete response (CR) or partial response (PR) as determined by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST)
Measured: up to 2 years
Changes in the level of serum tumor marker cancer antigen (CA) 19-9
changes evaluated via Fisher's exact tests or Wilcoxon rank sum tests, as appropriate
Measured: up to 2 years
Adverse events related to pulse dose erlotinib and gemcitabine
description, timing, grade (Common Terminology Criteria for Adverse Events Version 4.03 [CTCAE v4.03]), severity, seriousness, and relatedness
Measured: From the initiation of study treatment and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study startJul 2013
- Primary completion3 Sep 2020
- Study completion3 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies 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
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tony Reid, M.D., Ph.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, Tony Reid, M.D., Ph.D., University of California, San Diego
- Investigators
- Tony Reid, MD, PhD, Principal investigator, University of California Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02154737
- Sponsor's protocol ID
- 121359
- Status last verified
- Mar 2021
- First submitted
- 14 Jun 2013
- Last updated
- 2 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Dose Escalation Study of Gemcitabine and Pulse Dose Erlotinib in Second Line Treatment of Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT02154737
- Acronym / sponsor ID
- 121359
- Conditions
- Pancreatic Cancer
- Keywords
- Pancreatic, Gemcitabine, Gemzar, erlotinib, Tarceva
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Tony Reid, M.D., Ph.D.University, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jul 2013
- Primary completion
- 3 Sep 2020 (actual)
- Study completion
- 3 Sep 2020 (actual)
- First posted
- 3 Jun 2014 (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 purpose of this study is to see whether an altered schedule of giving erlotinib in combination with gemcitabine will be safe and might improve the results of the treatment for advanced cancer of the pancreas.
Gemcitabine and erlotinib are commercially available. Gemcitabine is FDA approved as first-line treatment for patients with locally advanced, unresectable or metastatic cancer of the pancreas. Erlotinib is FDA approved in combination with gemcitabine for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
The FDA recommended dose for erlotinib is 100 mg daily. This study will investigate the experimental administration of higher doses of erlotinib given for only three days twice a month, a schedule called "pulse dosing".
Detailed description
Survival of pancreatic cancer patients remains poor, and treatment with erlotinib remains one of the few agents that have demonstrated increased survival. Alternative dosing schedules for erlotinib should be explored since chronic low dose therapy fails to achieve therapeutically effective concentrations for many patients and leads to increased skin toxicity and may induce acquired resistance without significantly impacting the tumor. Therefore, higher doses given for shorter periods of exposure, similar to the dosing of most chemotherapeutic agents, may achieve more effective therapeutic doses of than chronic low dose therapy and may minimize skin toxicity observed with erlotinib.
No phase I studies have been done with the combination of high dose pulse erlotinib therapy with gemcitabine. We propose a phase I dose escalation study of three day oral dosing of erlotinib with standard dose (1000 mg/m2) gemcitabine. The starting dose of erlotinib is 750 mg, approximately 50% of the the dose found to be safe in previous combination studies with carboplatin and paclitaxel and with pemetrexed [Riely et al. 2009, Davies et al. 2009]. Since acquired resistance can occur rapidly and 5 to 7 days of treatment is not better than 3 days of treatment, we will focus on a 3 day high-dose pulse treatment given every 14 days. This will provide 11 days between erlotinib dosing for the recovery of normal tissues. Levels of serum erlotinib will also be monitored due to considerable interpatient variability in the metabolism of erlotinib.
The hypotheses of this study are:
- High-dose pulse therapy with erlotinib can be safely administered with standard dose gemcitabine.
- High-dose pulse therapy with erlotinib will permit recovery of the epidermis between treatments resulting in reduced skin toxicity compared to chronic daily dosing.
- Disease control with high-dose pulse therapy may be superior to that with chronic low dose therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| erlotinib and gemcitabine | Experimental | Drug: Gemcitabine, Drug: ErlotinibErlotinib will be administered orally on Days 2-4 and Days 16-18 of a 28-day cycle in serial cohorts with doses of 750mg, 1000mg, 1250mg, 1500mg, 1750mg, and 2000mg Gemcitabine will be administered intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Pathologically confirmed advanced pancreatic cancer defined as non-operable in a curative intent, locally recurrent, or metastatic disease.
- Measureable disease by (Response Evaluation Criteria in Solid Tumors) RECIST v1.1. Measureable lesions will be confirmed by radiological imaging.
- Progressive disease by (Response Evaluation Criteria in Solid Tumors) RECIST criteria during or after treatment with first-line chemotherapy (disease free interval must be less than 6 months) and have not received further second-line chemotherapy. Patients treated with prior chemo-radiation to the primary pancreatic tumor, for which the chemotherapeutic agent was used as a radio-sensitizing agent, are eligible.
- Age >18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0-2.
Key exclusion criteria (13 listed)
- Radiation within 4 weeks of study enrollment. Radiotherapy not permitted while on study. Exception: palliative radiotherapy of metastasis in extremities is allowed, but such lesions cannot be used as target or non-target lesions.
- Investigational compound within 4 weeks of enrollment or who are planning to receive other investigational drugs while participating in the study.
- Chemotherapy, biologics, immunotherapy, vaccine, cytokine therapy within 4 weeks prior to enrollment.
- Presence of untreated and/or symptomatic central nervous system (CNS) metastasis.
- Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, chronic renal disease, chronic pulmonary disease or active uncontrolled infection).
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 |
|---|---|---|
| GemcitabineAlso: GemzarGemcitabine will be administered intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. | Drug | erlotinib and gemcitabine |
| ErlotinibAlso: TarcevaErlotinib will be administered orally on Days 2-4 and Days 16-18 of a 28-day cycle in serial cohorts with doses of 750mg, 1000mg, 1250mg, 1500mg, 1750mg, and 2000mg. | Drug | erlotinib and gemcitabine |
Primary outcome
Rate of dose limiting toxicities of each subject
Time frame: 28 days
Rate will be assessed through summaries of adverse events, clinical laboratory abnormalities, and changes in physical exam and vital signs. All subjects who receive a single dose of study medication will be considered evaluable for safety.
5 secondary outcomes
Overall survival
Time frame: 2 years
progression-free survival
Time frame: Up to 2 years
Best tumor response
Time frame: up to 2 years
Changes in the level of serum tumor marker cancer antigen (CA) 19-9
Time frame: up to 2 years
Adverse events related to pulse dose erlotinib and gemcitabine
Time frame: From the initiation of study treatment and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier
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 2 Mar 2021.
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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.
Tony Reid, MD, PhD principal investigator
University of California Medical Center
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 Gemcitabine and Erlotinib in people with Pancreatic Cancer, run by Tony Reid, M.D., Ph.D. 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 9 inclusion and 13 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 2 Mar 2021. 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?
Rate of dose limiting toxicities of each subject (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Mar 2021.