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Pancreatic AdenocarcinomaPhase 2NCT01921751

High or Standard Intensity Radiation Therapy After Gemcitabine Hydrochloride and Nab-paclitaxel in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery

A Phase 2 study testing low intensity radiation therapy, Capecitabine and Gemcitabine in people with Pancreatic Adenocarcinoma and Stage III Pancreatic Cancer, run by Radiation Therapy Oncology Group at 46 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized phase II trial studies how well high or standard intensity radiochemotherapy after gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) work compared with gemcitabine hydrochloride and nab-paclitaxel alone in treating patients with pancreatic cancer that… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
low intensity radiation therapy, Capecitabine and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
46 sitesUnited States
Study dates
Aug 2013to Jun 2016
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

Who may be able to join

  • Histologically or cytologically proven diagnosis of adenocarcinoma of the pancreas prior to registration
  • Tumor diameter ≤ 7 cm
  • Unresectable by radiographic criteria (pancreas protocol CT or MRI) or exploration within 30 days prior to registration.
  • A cell block or core biopsy must be submitted for central review and analysis of SMAD4 status as soon as possible following step 1 registration.
  • No distant metastases, based upon the following minimum diagnostic workup:
  • History/physical examination within 30 days prior to registration
Show all 22Show fewer
  • Whole body fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG-PET/CT) within 30 days prior to registration NOTE: If whole-body FDG-PET/CT is not performed, CT of the chest and CT (or MRI) of abdomen and pelvis must be obtained (imaging of abdomen and pelvis need not be repeated if already included in pancreas protocol study)
  • Zubrod Performance Status 0-1 within 30 days prior to registration
  • Age ≥ 18;
  • Complete blood count (CBC)/differential obtained within 14 days prior to step 1 registration, with adequate bone marrow function defined as follows:
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 8.0 g/dl (NOTE: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
  • Additional laboratory studies within 14 days prior to registration:
  • carbohydrate antigen 19-9 (CA19-9); NOTE: in the event that a stent has been placed and biliary obstruction has been relieved, the CA19-9 should be drawn post stent placement
  • Creatinine < 2 mg/dl; Glomerular filtration rate (GFR) > 50 mL/min (Cockroft and Gault formula)
  • Bilirubin < 1.5 x ULN
  • Alanine aminotransferase (ALT) and aminotransferase (AST) ≤ 2.5 x ULN
  • Activated partial thromboplastin time (aPTT), prothrombin time (PT) ≤1.2 x upper limit of normal (ULN)
  • Patient must provide study specific informed consent prior to study entry
  • Women of childbearing potential and male participants must practice adequate contraception during protocol treatment and for at least 6 months following treatment
  • For females of child-bearing potential, negative serum pregnancy test within 30 days prior to registration

Who cannot join

  • More than one primary lesion
  • Prior invasive malignancy (unless disease free for a minimum of 1095 days [3 years]); Non-melanomatous skin cancer and previous early prostate cancer that had a non-rising prostate-specific antigen (PSA) are eligible
  • Prior systemic anti-cancer therapy for pancreatic cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiation therapy to the abdomen that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity, defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
Show all 15Show fewer
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients
  • Pregnancy or women of childbearing potential, women who cannot discontinue breastfeeding and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Prior allergic reaction to the study drug(s) involved in this protocol
  • Pre-existing Grade 2 or greater neuropathy
  • Distant metastases

Trial locations and contacts

46 sites in 1 country.

46 sites in 1 country

United States46 sites

  • Akron General Medical Center

    Akron, Ohio, 44307

  • McFarland Clinic PC-William R Bliss Cancer Center

    Ames, Iowa, 50010

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106-0995

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Sanford Clinic North-Bemidgi

    Bemidji, Minnesota, 56601

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

    Mount Holly, New Jersey, 08060

  • Intermountain Medical Center

    Murray, Utah, 84157

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Capital Health Medical Center-Hopewell

    Pennington, New Jersey, 08534

  • OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC

    Peoria, Illinois, 61615-7827

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Kaiser Permanente Cancer Treatment Center

    South San Francisco, California, 94080

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Door County Cancer Center

    Sturgeon Bay, Wisconsin, 54235-1495

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

Official title: A Phase II Randomized Trial Evaluating the Addition of High or Standard Intensity Radiation to Gemcitabine and Nab-paclitaxel for Locally Advanced Pancreatic Cancer

This randomized phase II trial studies how well high or standard intensity radiochemotherapy after gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) work compared with gemcitabine hydrochloride and nab-paclitaxel alone in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine, may make tumor cells more sensitive to radiation therapy. Giving radiation therapy in different ways and adding chemotherapy may kill more tumor cells. It is not yet known whether high intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel is more effective than standard intensity radiochemotherapy after gemcitabine hydrochloride and nab-paclitaxel or gemcitabine hydrochloride and nab-paclitaxel alone in treating pancreatic cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  • I. To determine if intensified radiochemotherapy following gemcitabine and nab-paclitaxel in patients with unresectable pancreatic cancer will show a signal for improved 2-year overall survival (OS) from 10% to 22.5% as compared to chemotherapy with gemcitabine and nab-paclitaxel alone.
  • II. To determine if standard radiochemotherapy, following gemcitabine and nab-paclitaxel, in patients with unresectable pancreatic cancer will show a signal for improved 2-year OS from 10% to 22.5% as compared to chemotherapy with gemcitabine and nab-paclitaxel alone.

SECONDARY OBJECTIVES:

  • I. To evaluate patterns of failure (local and systemic progression) by SMAD family member 4 (SMAD4) status and intensity of radiation therapy.
  • II. To evaluate the impact of radiochemotherapy on OS for the subset of SMAD4 intact patients.
  • III. To evaluate adverse events associated with the treatments.
  • IV. To evaluate correlation between SMAD4 status determined by immunohistochemistry (IHC) and genetic SMAD4 status.

Patients are randomized to 1 of 3 treatment arms.

After completion of study treatment, patients are followed up at 1 month and then every 3 months.

Being tested
low intensity radiation therapy, Capecitabine, Gemcitabine, high intensity radiation therapy, nab-Paclitaxel
Keywords
SMAD4, IMRT, gemcitabine, high-dose radiotherapy
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • low intensity radiation therapyRadiation

    Also called 3-dimensional conformal radiation therapy, 3-dimensional radiation therapy, 3D-CRT, Conformal Therapy

    50.4 Gy in 28 1.8 Gy fractions (IMRT or 3D-CRT), 5 days/week, starting 3-5 weeks after the last dose of induction chemotherapy

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    825 mg/m2 PO twice daily, 5 days/week, beginning on the first day of radiation therapy and ending on the last day of radiation therapy.

  • GemcitabineDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, GEMCITABINE HYDROCHLORIDE, Gemzar

    1000 mg/m2 weekly as a 30 minute infusion after nab-Paclitaxel, three weeks on and 1 week off [1 cycle = 4 weeks]

  • high intensity radiation therapyRadiation

    Also called IMRT, Intensity Modulated RT, intensity-modulated radiation therapy, Intensity-Modulated Radiotherapy

    63 Gy intensity-modulated radiation therapy (IMRT) in 28 2.25 Gy fractions, 5 days/week, starts 3-5 weeks after the last dose of induction chemotherapy

  • nab-PaclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    125 mg/m2 weekly as a 30-40 minute infusion, three weeks on and 1 week [1 cycle = 4 weeks]

Study groups in NCT01921751
Study groupRoleWhat they receive
Chemotherapy + high intensity radiationExperimentalInduction chemotherapy with four cycles of gemcitabine and nab-paclitaxel [randomized to this arm after 3rd cycle and no progression]; followed by concurrent high intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity
Receives: Drug: Capecitabine; Drug: Gemcitabine; Radiation: high intensity radiation therapy; Drug: nab-Paclitaxel
Chemotherapy + low intensity radiationExperimentalInduction chemotherapy with four cycles of gemcitabine and nab-paclitaxel [randomized to this arm after 3rd cycle and no progression]; followed by concurrent low intensity radiation therapy and capecitabine; followed by consolidation chemotherapy with gemcitabine and nab-paclitaxel until progression or unacceptable toxicity
Receives: Radiation: low intensity radiation therapy; Drug: Capecitabine; Drug: Gemcitabine; Drug: nab-Paclitaxel
ChemotherapyActive comparatorGemcitabine and nab-paclitaxel until progression or unacceptable toxicity [randomized to this arm after 3rd cycle and no progression]
Receives: Drug: Gemcitabine; Drug: nab-Paclitaxel

What is being measured

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

  1. Overall Survival

    Survival time is defined as time from randomization to date of death from any cause and was to be estimated by the Kaplan-Meier method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients last reported to be alive at time of study termination is reported.

    Measured: From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.

Secondary outcomes (3)

  1. Overall Survival Within SMAD4 Subsets

    Survival time is defined as time from randomization to date of death from any cause and was to be estimated by the Kaplan-Meier method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients last reported to be alive at time of study termination is reported. Patients are categorized by SMAD4 status of "intact" (positive nuclear labeling is observed of the neoplastic cells ), "loss" (no labeling observed of the neoplastic cells) , or "undetermined" (insufficient material for immunostaining or results are equivocal). This study terminated early with only 20 registered (346 planned) and 13 randomized (288 planned). There are no proven results as to which category has better incomes, but this study hypothesizes that "intact" is highly correlated with local failures and "loss" is highly correlated with widespread metastasis, in which case "intact" would correspond with positive results relative to "loss".

    Measured: From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.

  2. Patterns of Failure (Local and Metastatic Failure)

    Local progression is defined as least a 20% increase in the sum of diameters of the primary, taking as reference the baseline sum. Given the inherent inaccuracy in determining size of a primary pancreatic carcinoma, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and progression must be demonstrated on at least two sequential scans. Metastatic failure is defined as metastatic disease. Local and distant failure were to be estimated by the cumulative incidence method. Given the limited follow-up due to early closure and termination of data collection, only the number of patients with failure is reported.

    Measured: From randomization until last follow-up. Maximum follow-up at time of study termination was 8.3 months.

  3. Correlation Between SMAD4 Status Determined by Immunohistochemistry (IHC) and Genetic SMAD4 Status

    Measured: Baseline

Timeline

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

  1. First posted13 Aug 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionJun 2016
  4. Study completionJun 2016

Why it stopped: Trial would not be completed in a reasonable timeframe per CTEP guidelines

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01921751
Sponsor's protocol ID
RTOG 1201
Other IDs
NCI-2013-01280, RTOG 1201, RTOG-1201, U10CA180868, U10CA021661
Status last verified
Jun 2018
First submitted
9 Aug 2013
Last updated
13 Jul 2018
Data monitoring committee
Yes

Publications

  • Jani A, Horowitz DP. Radiation Therapy Deviations in Trial of Locally Advanced Pancreatic Cancer [corrected]. JAMA. 2016 Oct 4;316(13):1409. doi: 10.1001/jama.2016.9778. No abstract available.

    PubMed 27701653

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing low intensity radiation therapy, Capecitabine and Gemcitabine in people with Pancreatic Adenocarcinoma and Stage III Pancreatic Cancer, run by Radiation Therapy Oncology Group at 46 sites 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 22 inclusion and 15 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: stopped early, as of the sponsor's last update on 13 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites 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 22 Mar 2018). 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?

Overall Survival (time frame: From randomization until last follow-up. Analysis was to occur after a total of 140 deaths were reported within the pairing of each radiation arm with the chemotherapy alone arm. Maximum follow-up at time of study termination was 8.3 months.). 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 NCT01921751, 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 13 Jul 2018.

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