Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    02890355
Previous Study | Return to List | Next Study

FOLFIRI or Modified FOLFIRI and Veliparib as Second Line Therapy in Treating Patients With Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02890355
Recruitment Status : Active, not recruiting
First Posted : September 7, 2016
Results First Posted : September 29, 2020
Last Update Posted : February 10, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This randomized phase II trial studies how well modified irinotecan hydrochloride, leucovorin calcium, fluorouracil (FOLFIRI) and veliparib as a second line of therapy work compared to FOLFIRI in treating patients with pancreatic cancer that has come back after a period of improvement (metastatic). Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether modified FOLFIRI and veliparib as second line therapy is more effective than FOLFIRI alone in treating metastatic pancreatic cancer.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Recurrent Pancreatic Carcinoma Stage IV Pancreatic Cancer AJCC v6 and v7 Drug: Fluorouracil Drug: Irinotecan Hydrochloride Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Veliparib Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the overall survival (OS) of metastatic pancreatic cancer patients treated with fluorouracil, irinotecan (irinotecan hydrochloride), leucovorin (leucovorin calcium), (modified FOLFIRI) and ABT-888 (veliparib) compared to a control arm of fluorouracil, irinotecan, and leucovorin (FOLFIRI).

SECONDARY OBJECTIVES:

I. To evaluate the frequency and severity of toxicity associated with each of the treatment arms in this patient population.

II. To evaluate the progression-free survival (PFS) in each of the treatment arms in this patient population.

III. To evaluate the overall response rate (confirmed and unconfirmed; complete response + partial response), disease control rate (confirmed and unconfirmed; complete response + partial response + stable disease), and duration of response in each of the treatment arms in this patient population.

TERTIARY OBJECTIVES:

I. To evaluate if breast cancer, early onset (BRCA)1 and BRCA2 mutations (somatic or germline) are associated with improved clinical outcomes (overall survival [OS], progression-free survival [PFS] and overall response rates [ORR]) in each treatment arm.

II. To evaluate the impact of homologous recombination deficiency (HRD) score on clinical outcomes in each treatment arm.

III. To evaluate the impact of genomic alterations identified by the BROCA-homologous recombinant (HR) assay, other than BRCA1/2, on clinical outcomes in each treatment arm.

IV. To bank tissue for future translational medicine studies.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive veliparib orally (PO) twice daily (BID) every 12 hours on days 1-7, irinotecan hydrochloride intravenously (IV) over 90-120 minutes on day 3, leucovorin calcium IV over 90-120 minutes on day 3, and fluorouracil IV over 46 hours on days 3-5.

ARM II: Patients receive irinotecan hydrochloride IV over 90-120 minutes on day 1, leucovorin calcium IV over 90-120 minutes on day 1, and fluorouracil IV bolus over 15 minutes on days 1 and then over 46 hours on days 1-3.

In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of 2nd Line FOLFIRI Versus Modified FOLFIRI With PARP Inhibitor ABT-888 (Veliparib) (NSC-737664) in Metastatic Pancreatic Cancer
Actual Study Start Date : September 1, 2016
Actual Primary Completion Date : May 1, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Arm I (veliparib and mFOLFIRI)
Patients receive veliparib PO BID every 12 hours on days 1-7, irinotecan hydrochloride IV over 90-120 minutes on day 3, leucovorin calcium IV over 90-120 minutes on day 3, and fluorouracil IV over 46 hours on days 3-5.
 Drug: Fluorouracil
Given IV
Other Names:
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • Irinotecan Hydrochloride Trihydrate
  • Irinotecan Monohydrochloride Trihydrate
  • U-101440E

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Leucovorin Calcium
Given IV
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
Active Comparator: Arm II (FOLFIRI)
Patients receive irinotecan hydrochloride IV over 90-120 minutes on day 1, leucovorin calcium IV over 90-120 minutes on day 1, and fluorouracil IV bolus over 15 minutes on days 1 and then over 46 hours on days 1-3.
 Drug: Fluorouracil
Given IV
Other Names:
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Drug: Fluorouracil
Given IV bolus
Other Names:
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • Irinotecan Hydrochloride Trihydrate
  • Irinotecan Monohydrochloride Trihydrate
  • U-101440E

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Leucovorin Calcium
Given IV
Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 3 years ]

    OS: time to death by any cause from randomized treatment arm assignment.

    The log-rank test with stratification was used by prior systemic treatment for metastatic disease. Distributions of overall survival in arms 1 and 2 were estimated using the method of Kaplan-Meier.



Secondary Outcome Measures :
  1. Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Duration of treatment and follow up until death or 3 years post registration ]
    Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

  2. Progression Free Survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]
    From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact.

  3. Overall Response Rate, ORR [ Time Frame: Up to 3 years post registration ]
    Overall response rate (ORR) is defined as the proportion of participants who have a confirmed and unconfirmed, partial or complete response to therapy.

  4. Disease Control Rate [ Time Frame: Up to 3 years post registration ]
    Disease control rate (DCR) is defined as the proportion of participants who have a confirmed and unconfirmed, partial, complete or stable response to therapy.

  5. Duration of Response (DoR) [ Time Frame: Up to 3 years post registration ]

    DoR: time from date of first documentation of response (complete response, CR, or partial response, PR) to date of first documentation of progression or symptomatic deterioration, or death due to any cause among participants, who achieve a response (CR or PR).

    The distribution of DoR in each treatment arm will be estimated using the Kaplan-Meier method.



Other Outcome Measures:
  1. Prevalence of BRCA1 and BRCA2 Mutations (Somatic or Germline) [ Time Frame: Baseline ]
    BRCA1/2 mutations will be associated with clinical outcomes (OS, PFS, and overall response rate [ORR]).

  2. Homologous Recombination Deficiency (HRD) Score [ Time Frame: Baseline ]
    The impact of HRD positivity will be evaluated on clinical outcomes in each treatment arm. The HRD score is the unweighted sum of loss of heterozygosity footprint, telomeric allelic imbalance, and large-scale state transitions measurements on a scale from 0-100. The HRD score threshold for positivity in this population will be estimated by applying receiver operating characteristic curves, classifying patients by overall disease response.

  3. Genomic Alterations Identified by the BROCA-homologous Recombinant (HR) Assay [ Time Frame: Baseline ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically documented pancreatic adenocarcinoma; patients with pancreatic neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible
  • Patients must have metastatic disease that is measurable; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form
  • Patients must not have history of brain metastases
  • Patients must have had one and only one prior regimen of systemic therapy for metastatic disease unless the patient meets the criteria below
  • Prior systemic therapy and chemoradiotherapy for treatment of resectable, borderline resectable or locally advanced unresectable disease is allowed and does not count toward prior therapy for metastatic disease
  • Patients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable or borderline/locally advanced unresectable disease and progressed with metastatic disease within 3 months of the past dose of systemic therapy are eligible
  • Patients must have completed systemic therapy at least 14 days prior to registration, any surgical procedure must have been performed at least 14 days prior to registration, and radiation therapy must be completed at least 7 days prior to registration; patients must have recovered from major side effects of prior therapies or procedures in the opinion of the local site investigator prior to registration
  • Patients must not have received prior irinotecan-based chemotherapy (e.g. irinotecan hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFIRINOX] or FOLFIRI)
  • Patients must not have received prior PARP inhibitor therapy including, but not limited to ABT-888, olaparib, rucaparib, and talazoparib (BMN637)
  • Patients must have a Zubrod performance status of 0-1
  • Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,500/mcL
  • Within 14 days prior to registration: Hemoglobin >= 9 g/dL
  • Within 14 days prior to registration: Platelets >= 100,000/mcL
  • Within 14 days prior to registration: Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Within 14 days prior to registration: Serum albumin >= 3.0 g/dL
  • Within 14 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN; patients with liver metastases may have AST and ALT of =< 5.0 x IULN
  • Within 14 days prior to registration: Serum creatinine =< 2.0 mg/dL
  • Patients must have CA19-9 obtained within 14 days prior to registration; if CA19-9 is normal a carcinoembryonic antigen (CEA) must be tested within 14 days prior to registration
  • Patients must have blood urea nitrogen (BUN), alkaline phosphatase, sodium, potassium, calcium, glucose, chloride, and bicarbonate levels obtained within 14 days prior to registration
  • Patients must not have any clinically significant and uncontrolled major medical condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea; active uncontrolled infection; symptomatic congestive heart failure (New York Heart Association [NYHA] class >= II); unstable angina pectoris or cardiac arrhythmia; psychiatric illness/social situation that would limit compliance with study requirements
  • Patients must not have active seizure or history of seizure
  • Patients must be able to swallow whole capsule
  • Patients must have a complete physical examination and medical history within 28 days prior to registration
  • Patients must not have known Gilbert's syndrome
  • Patients must not have known hypersensitivity to irinotecan, fluorouracil, or leucovorin
  • Patients of childbearing potential must have a negative pregnancy test within 28 days prior to registration and must not be nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method during the study and for 6 months following completion of treatment; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients must be willing and able to undergo a biopsy after signed consent and prior to registration; patients must have tumor tissue and blood samples available and be willing to submit tumor and blood samples; NOTE: core biopsy required; fine needle aspiration (FNA) is not an acceptable substitute for core biopsy
  • If archival tumor is available for submission, patients must be willing to submit tumor sample
  • Patients must be offered the opportunity to participate in specimen banking for future use
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02890355


Locations
Show Show 789 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Elena G Chiorean Southwest Oncology Group
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan  [PDF] June 6, 2018

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02890355    
Other Study ID Numbers: NCI-2015-02248
NCI-2015-02248 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1513
S1513 ( Other Identifier: SWOG )
S1513 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2016    Key Record Dates
Results First Posted: September 29, 2020
Last Update Posted: February 10, 2021
Last Verified: January 2021
Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Calcium, Dietary
Leucovorin
Folic Acid
Fluorouracil
Irinotecan
Veliparib
Camptothecin
 Calcium
Levoleucovorin
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes