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Pancreatic CancerPhase 1NCT01296763

Trial of ICM With or Without AZD2281 (Olaparib) in Patients With Advanced Pancreatic Cancer

A Phase 1 study testing Irinotecan, Cisplatin and Olaparib (for levels 1 and 5) in people with Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites 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

Patients whose pancreatic cancers have defects in the BRCA/Fanconi DNA repair pathway or other defects in homologous repair will have cancers that respond to olaparib when given in combination with the DNA damaging agents, irinotecan, cisplatin, mitomycin C (ICM). 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?
Irinotecan, Cisplatin and Olaparib (for levels 1 and 5)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
2 sitesUnited States
Study dates
Jan 2011to Feb 2016
Phase
Phase 1
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

  • Provision of fully informed consent prior to any study specific procedures.
  • Histologic or cytologic confirmation of exocrine pancreatic adenocarcinoma.
  • Locally advanced, inoperable (due to venous or arterial encasement ≥ 180° of the vessel), and/or metastatic disease by imaging (CT, MRI, or EUS). Acquisition of tissue rather than cytology is encouraged if the patient gives informed consent.
  • Measurable disease according to RECIST 1.1 criteria
  • Prior neoadjuvant or adjuvant therapy is acceptable, as long as no more than one drug of the ICM regimen was used.
  • No prior chemotherapy for advanced pancreatic cancer with Olaparib is permitted. Gemzar, Tarceva, and 5-FU or Xeloda, Oxaliplatin Taxotere, and FOLFIRINOX are permitted.
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  • Three weeks since last surgery or chemotherapy mentioned in #5 above or investigational therapies. Four weeks since radiation.
  • No prior PARP inhibitors of any type
  • ECOG status < 3
  • Life expectancy > 3 months
  • Patients must have normal organ and bone marrow function
  • Age >=18.
  • Patient is willing and able to comply with the protocol for the duration of the study including treatment, scheduled visits, and examinations.
  • Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1
  • For inclusion in genetic research, patients must fulfill the following criterion:
  • Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.

Who cannot join

  • Patients with second primary cancer, except: adequately treated non-melanoma skin cancer or curatively treated in-situ solid tumors with no evidence of disease for ≥ 5 years.
  • Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), less than 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases before and during the study as long as these were started at least 4 weeks prior to treatment.
  • For patients who have locally advanced pancreatic cancer only, if they have received therapeutic doses of radiation therapy to their pancreatic bed (~50 Gy) for treatment of their locally advanced pancreatic cancer
  • Patients having already had prior chemotherapy for more than 12 months for their advanced pancreatic cancer (not including adjuvant/neoadjuvant)
  • Patients receiving the following classes of inhibitors of CYP3A4 (see Section for guidelines and wash out periods).
  • Current use of azole antifungals, macrolide antibiotics, or protease inhibitors
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  • Unresolved toxicities (>CTCAE 4.0 grade 2) caused by previous cancer therapy.
  • Patients with known brain metastases. A scan to confirm the absence of brain metastases is not required unless the initial examination reveals CNS signs of disease.
  • Major surgery less than 3 weeks prior to starting study treatment and patients must have recovered from any effects of any major surgery.
  • Patients considered a poor medical risk due to serious, uncontrolled medical disorders, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  • Patients unable to swallow oral medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Breast feeding and/or pregnant women.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Patients with known active hepatic disease (i.e., Hepatitis B or C). Patients with a known hypersensitivity to Olaparib or any of the excipients of the product or history of severe allergic reactions to platinums or chemotherapy.
  • Grade 2 neuropathy at entry from any etiology, including diabetes (in view of Cisplatin).
  • Prior episodes of recurrent deep vein thrombosis or Trousseau's Syndrome unless the patient is successfully anticoagulated. If a patient has had a history of clotting or is suspected to have Trousseau's syndrome and is not anticoagulated, a D-Dimer level will be checked. If it is > 3 x ULN, patients will be expected to be anticoagulated with low molecular weight heparinoids (i.e. Lovonox).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • The Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21231

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: A Randomized Multi-center Phase I/II Trial of ICM (Irinotecan, Cisplatin, Mitomycin C) With or Without AZD2281 (Olaparib) in Patients With Advanced Pancreatic Cancer

Patients whose pancreatic cancers have defects in the BRCA/Fanconi DNA repair pathway or other defects in homologous repair will have cancers that respond to olaparib when given in combination with the DNA damaging agents, irinotecan, cisplatin, mitomycin C (ICM).

Read the detailed description

The trial is designed to evaluate the role of Parp inhibitor based therapy, combining the most well studied and potent Parp inhibitor currently available with a low-dose combination of DNA damaging agents to optimize the effects of Parp inhibition. To ensure optimal response rates in the trial, to enrich our population for patients likely to achieve the best clinical response to Parp inhibitor based therapy, we will recruit and enroll patients with known BRCA mutations, patients of Jewish ancestry, patients with familial pancreatic cancer, as well as with sporadic pancreatic cancer. We will test patients and their cancers for other inherited or acquired defects in homologous DNA repair. For the phase 1 study, we will enroll up to 30 patients. For the phase 2 component of the study, 100 patients with locally, advanced, unresectable or metastatic pancreatic cancer will be enrolled. An initial phase I analysis will be performed to test the safety of the ICM with Olaparib regimen at the doses we predict will be effective for the phase 2 and ensure that these doses are below the maximum tolerated dose. For this phase 1 we will use a standard 3+3 design and will test the following dose regimens in a 28 day cycle:

Dose level 1: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib (100 mg bid p.o., Day 1 \& Day 8) Dose level 2: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 100 bid p.o. day 1-3, day 8-10 (if this dose is not tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 1) Dose level 3: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 200 bid p.o.day 1-3, day 8-10 (if this dose is not tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 2) Dose level 4: Cisplatin/Irinotecan i.v.(day 1, 8) and Olaparib 200 bid p.o. day 1-12 (if this dose is not tolerated, go to Dose 5: Mitomycin + Olaparib Dose level 3)) Dose level 5: Cisplatin/Irinotecan i.v.(day 1, 8), Mitomycin Day 1 (5 mg/m2 IV), along with the established tolerated dose level of Olaparib.

Other intermediate dose schedules of Olaparib may be considered to achieve the most optimal tolerable regimen" If there are DLTs at Dose 1, we will reduce the duration of Olaparib

Note: The Principal Investigator and Astrazeneca decided not to move forward with the Phase II part of the study. Therefore the arms of Irinotecan, Cisplatin, Mitomycin C with Olaparib versus Irinotecan, Cisplatin, Mitomycin C without Olaparib will not be compared.

Being tested
Irinotecan, Cisplatin, Olaparib (for levels 1 and 5), Olaparib (for dose level 2), Mitomycin-C
Keywords
Irinotecan, Cisplatin, Carboplatin, Mitomycin-C, Olaparib, AZD2281
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • IrinotecanDrug

    Irinotecan 70 mg/m2 IV, Days 1 and 8

  • CisplatinDrug

    Cisplatin 25 mg/m2 IV, Days 1 and 8

  • Olaparib (for levels 1 and 5)Drug

    Olaparib 100 mg bid oral, Days 1 and 8

  • Olaparib (for dose level 2)Drug

    Olaparib 100mg bid oral, Day 1-3, Day 8-10

  • Mitomycin-CDrug

    Mitomycin 5 mg/m2 IV, Day 1

Study groups in NCT01296763
Study groupRoleWhat they receive
Irinotecan, Cisplatin, Olaparib, then add Mitomycin-CExperimentalA 3+3 dose escalation design will be used starting with dose 1. The maximally tolerated dose is defined as the highest dose for which at most 1 out of 6 patients experiences a DLT. We will use 3 patients per dose cohort. If 0 of 3 patients have a DLT (see section 5a) then the escalation will be continued at the next dose level. If 1 of 3 patients have a DLT then three more patients will be enrolled at this dose. If 1 of 6 patients has a DLT then the dose escalation will continue. If 2 or more of the first 3 patients, or >2 of 6 patients treated have a DLT at the dose level, we will reduce the dose to the previous dose level of Olaparib for the phase 2 and then test Mitomycin C (phase 1 dose 5). If DLTs are observed at our dose 1 regimen, we will reduce the duration of Olaparib from day 1 and day 8 to just day 1 (dose level -1) and we will not test Mitomycin C in the trial.
Receives: Drug: Irinotecan; Drug: Cisplatin; Drug: Olaparib (for levels 1 and 5); Drug: Olaparib (for dose level 2); Drug: Mitomycin-C

What is being measured

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

  1. Number of Participants Who Experienced a Dose Limiting Toxicity to Determine the Maximum Tolerated Dose (MTD)

    1.Phase I - Assess the safety and toxicities of IC with Olaparib escalating to ICM with Olaparib in patients with locally advanced and metastatic pancreatic cancer and determine the phase 2 dose. The number of subjects who experienced a dose limiting toxicity was assessed.Dose-limiting toxicity (DLT) is defined as any of the following study drug-related events experienced during Cycle 1:

    Thrombocytopenia with platelets <25,000 x106/l > 7 days. Grade 4 neutropenia lasting ≥7 days. Grade 3 or 4 febrile neutropenia. Grade 3 or greater non-haematological toxicities; excluding grade 3 diarrhoea, nausea or vomiting despite adequate treatment and grade 3 fatigue, lethargy and GGT elevation.

    Delay of >2 weeks for next scheduled IC/ICM for reasons of toxicity.

    Measured: 2 years

Secondary outcomes (1)

  1. Number of Years From Cycle 1, Day 1 On-Study to Date of Death

    The overall survival of subjects with locally advanced and/or metastatic pancreatic cancer treated with Irinotecan, Cisplatin, Olaparib, with escalation to the addition of Mitomycin-C. Survival from cycle 1, day 1 on-study to date of death was assessed.

    Measured: 5 years

Timeline

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

  1. First posted15 Feb 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionJan 2014
  4. Study completionFeb 2016

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01296763
Sponsor's protocol ID
J1070
Other IDs
RC2CA148346-01, NA_00032826
Status last verified
Feb 2016
First submitted
21 Jan 2011
Last updated
22 Mar 2016
Data monitoring committee
Yes

Publications

  • Yarchoan M, Myzak MC, Johnson BA 3rd, De Jesus-Acosta A, Le DT, Jaffee EM, Azad NS, Donehower RC, Zheng L, Oberstein PE, Fine RL, Laheru DA, Goggins M. Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. Oncotarget. 2017 Jul 4;8(27):44073-44081. doi: 10.18632/oncotarget.17237.

    PubMed 28454122

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Irinotecan, Cisplatin and Olaparib (for levels 1 and 5) in people with Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 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 16 inclusion and 16 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 22 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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?

Yes. Results are posted in the registry (first posted 22 Mar 2016). 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?

Number of Participants Who Experienced a Dose Limiting Toxicity to Determine the Maximum Tolerated Dose (MTD) (time frame: 2 years). 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 NCT01296763, 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 22 Mar 2016.

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