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Adenocarcinoma of the PancreasPhase 1NCT01068327

Stereotactic Radiation, Nelfinavir Mesylate & Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

A Phase 1 study testing gemcitabine hydrochloride, leucovorin calcium and fluorouracil in people with Adenocarcinoma of the Pancreas and Stage III Pancreatic Cancer, run by University of Nebraska at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of stereotactic radiation therapy and nelfinavir mesylate when given together with gemcitabine hydrochloride, leucovorin calcium, and fluorouracil in treating patients with locally advanced pancreatic cancer. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
gemcitabine hydrochloride, leucovorin calcium and fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
5 Nov 2007to 1 Feb 2015
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The time between other investigational agents and enrollment on this study is at least 30 days
  • Pathologically confirmed adenocarcinoma of the pancreas
  • Patients have localized or locally advanced disease with no evidence of distant metastases
  • The maximum dimension of the tumor must be =< 8 cm
  • Karnofsky Performance Status of 60% or better
  • Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
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  • Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
  • Patients who received radiation therapy > 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
  • All malignant disease must be able to be encompassed within a single irradiation field
  • All patients must have radiographically assessable disease
  • Patients must have a absolute granulocyte count (AGC) greater than or equal to 1500/uL and platelet count greater than or equal to 100,000/uL
  • Patients must have a serum creatinine less than or equal to 2 mg/dL and total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction
  • If the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of biliary stent (7 French or greater) or percutaneous transhepatic drainage are acceptable; once biliary drainage has been established, institution of gemcitabine therapy may proceed when the total bilirubin falls to below 4.0 mg/dL
  • The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
  • Patients may have had prior chemotherapy for pancreatic cancer
  • Any prior therapy is acceptable except radiation to the abdomen

Who cannot join

  • Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: carbamazepine; phenobarbital; phenytoin; rifabutin; sildenafil; atorvastatin; cyclosporine; tacrolimus; sirolimus; methadone; ethinyl estradiol; azithromycin
  • Patients who can not undergo staging laparoscopy and marker implantation; this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful
  • The patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy
  • History of allergy to chemotherapy agents or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
  • Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
  • Patients with human immunodeficiency virus (HIV) infection, or hepatic insufficiency
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  • Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with NFV (nelfinavir mesylate)
  • Patients who can not take oral medications
  • Patients with active duodenal ulcer or bleeding or history of a gastrointestinal fistula or perforation or other significant bowel problems (severe nausea, vomiting, inflammatory bowel disease and significant bowel resection)
  • Patients with prior malignancy will be excluded EXCEPT for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
  • Patients receiving the following drugs that are contraindicated with NFV will be excluded: amiodarone; quinidine; rifampin; dihydroergotamine; ergonovine; ergotamine; methylergonovine; St. John's wort (hypericum perforatum); lovastatin; simvastatin; pimozide; midazolam; triazolam
  • Pregnant and nursing women are excluded from this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: A Phase 1 Study of Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir as Part of a Neoadjuvant Regimen in Patients With Locally Advanced Pancreatic Cancer

This phase I trial is studying the side effects and best dose of stereotactic radiation therapy and nelfinavir mesylate when given together with gemcitabine hydrochloride, leucovorin calcium, and fluorouracil in treating patients with locally advanced pancreatic cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs, such as nelfinavir mesylate, may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as gemcitabine hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving stereotactic radiation therapy and nelfinavir mesylate together with combination chemotherapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish the safety, dose-limiting toxicities and maximally tolerated dose of hypofractionated stereotactic radiotherapy concurrently with nelfinavir in patients with locally advanced pancreatic cancer given as part of a neoadjuvant chemoradiation therapy regimen.

SECONDARY OBJECTIVES:

  1. To evaluate the surgical complete resection rate. II. To evaluate the pathological response. III. To evaluate tumor response on computed tomography (CT)/magnetic resonance imaging (MRI).

IV. To evaluate the correlation between the radiologic response and pathologic response.

TERTIARY OBJECTIVES:

  1. To measure phospho-AKT expression in pancreatic tumor tissue prior to and following the neoadjuvant chemo-radiation program. (Correlative) II. To measure nelfinavir pharmacokinetics at steady-state. (Correlative) III. To measure the pharmacogenomic status of CYP2C19*2 (G681A) in the study population. (Correlative)

OUTLINE: This is a dose-escalation study of stereotactic radiotherapy (SRT) and concurrent nelfinavir mesylate.

NEOADJUVANT THERAPY: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes, leucovorin calcium IV over 30 minutes, and fluorouracil IV continuously over 24 hours on days 1 and 8. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive nelfinavir mesylate orally (PO) twice daily (BID) beginning in week 9 and continuing until the completion of SRT or until 14 days after the completion of SRT. Patients undergo concurrent SRT once daily for 5 days in week 11.

SURGERY AND ADJUVANT CHEMOTHERAPY: Approximately 2-3 weeks after completion of SRT, patients undergo restaging to evaluate disease response. Patients with resectable or potentially resectable disease and no metastasis undergo definitive surgery 2-3 weeks later. Approximately 1 month after surgery, these patients receive three additional courses of gemcitabine hydrochloride, leucovorin calcium, and fluorouracil as above. Patients with unresectable disease that is stable or responsive at the time of surgical exploration may resume treatment with gemcitabine hydrochloride, leucovorin calcium, and fluorouracil as above in the absence of disease progression or unacceptable toxicity. Patients with metastatic disease at the time of restaging are removed from the study.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01068327
Study groupRoleWhat they receive
Treatment (SRT, radiosensitizer, and chemotherapy)ExperimentalSee Detailed Description
Receives: Drug: gemcitabine hydrochloride; Drug: leucovorin calcium; Drug: fluorouracil; Drug: nelfinavir mesylate; Radiation: stereotactic body radiation therapy; Radiation: hypofractionated radiation therapy; Procedure: therapeutic conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

    Due to delayed toxicities attributable to radiotherapy, all toxicities observed within 1 month of surgery will be scored. Toxicity will be graded and tabled by dose levels.

    Measured: Within 1 month of surgery

  2. Maximally tolerated dose (MTD) of stereotactic radiotherapy and concurrent nelfinavir mesylate

    The MTD of SRT/nelfinavir mesylate is defined as the highest dose level at which no greater than one dose-limiting toxicity is observed in 6 patients.

    Measured: 3 patients will initially be treated at each dose level (4 levels); a minimum of 1 month of observation after surgery is required in all 3 patients before escalation

Secondary outcomes (7)

  1. Rate of complete surgical resection

    At the MTD, the rate of surgical complete resection with 90% exact binomial confidence intervals will be calculated.

    Measured: At the time of surgery (2-3 weeks after completion of SRT)

  2. Pathological response

    At the MTD, the rate of pathologic response with 90% exact binomial confidence intervals will be calculated.

    Measured: Pre- to post-treatment

  3. Tumor response on CT/MRI

    Pre- to post-treatment changes in tumor size on CT or MRI scan (if CT is not sufficient).

    Measured: Change from pre- to post-treatment

  4. Radiologic response and pathologic response

    Correlation between the radiologic response and pathologic response

    Measured: Pre- to post-treatment

  5. Phospho-AKT expression in pancreatic tumor tissue (correlative)

    Exploratory analyses will compare pre- to post-nelfinavir mesylate treatment changes in Akt levels between patients who achieve or do not achieve R0 resection by the nonparametric Wilcoxon rank sum test.

    Measured: Pre- to post-nelfinavir mesylate

  6. Pharmacokinetics of nelfinavir mesylate (correlative)

    The data will be modeled using WinNonLin Pro version 4.1. The pharmacokinetic parameters will be presented as the mean and standard deviation.

    Measured: After at least 1 week of NFV: *0 h (trough); *After NFV dosing: 1, 2, 3, 4, 5, 6, 8, and 12 h

  7. Pharmacogenomic status of CYP2C19*2 (G681A) (correlative)

    There is currently insufficient clinical data to indicate whether any of the specific polymorphisms proposed to be studied, particularly those subjects with a heterozygous state, will correlate with meaningful differences in the pharmacokinetic parameters of nelfinavir mesylate. These analyses must therefore be exploratory in nature.

    Measured: Enrollment, at the time of planned tumor tissue procurement, and at the time that re-staging studies are done

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2010 (estimated)
  2. Study start5 Nov 2007
  3. Primary completion1 Aug 2013
  4. Study completion1 Feb 2015

Resources

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
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01068327
Sponsor's protocol ID
0441-07-FB
Other IDs
NCI-2009-01443, P30CA036727
Status last verified
Oct 2023
First submitted
25 Jan 2010
Last updated
10 Oct 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lin C, Verma V, Ly QP, Lazenby A, Sasson A, Schwarz JK, Meza JL, Are C, Li S, Wang S, Hahn SM, Grem JL. Phase I trial of concurrent stereotactic body radiotherapy and nelfinavir for locally advanced borderline or unresectable pancreatic adenocarcinoma. Radiother Oncol. 2019 Mar;132:55-62. doi: 10.1016/j.radonc.2018.11.002. Epub 2018 Dec 20.

    PubMed 30825970

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing gemcitabine hydrochloride, leucovorin calcium and fluorouracil in people with Adenocarcinoma of the Pancreas and Stage III Pancreatic Cancer, run by University of Nebraska 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 16 inclusion and 12 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 10 Oct 2023. 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?

Dose-limiting toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (time frame: Within 1 month of surgery). The study lists 2 primary outcomes in all. 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 NCT01068327, 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 10 Oct 2023.

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