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A Randomized Phase II Trial of Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT02879318
Recruitment Status : Active, not recruiting
First Posted : August 25, 2016
Last Update Posted : July 30, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Brief Summary:
The standard or usual treatment for this disease consists of two chemotherapy drugs gemcitabine and nab-paclitaxel given together.

Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Drug: Gemcitabine Drug: Nab-paclitaxel Drug: Durvalumab Drug: Tremelimumab Phase 2

Detailed Description:

Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and reactivate the immune response. This may halp to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatments alone.

Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab.

Combination of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone and while the combination has been studied in a few people, it is not clear if it can offer better results than standard treatment.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma
Study Start Date : August 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Gemcitabine plus Nab-Paclitaxel
Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 7, 15 Q28 days.
Drug: Gemcitabine
Drug: Nab-paclitaxel
Experimental: Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab

Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 7, 15 Q28 days.

plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity.

Drug: Gemcitabine
Drug: Nab-paclitaxel
Drug: Durvalumab
Drug: Tremelimumab



Primary Outcome Measures :
  1. Overall survival (Phase III) [ Time Frame: 35 months ]

Secondary Outcome Measures :
  1. Progression free survival defined as the time from randomization to the first objective documentation of disease progression or death due to any cause [ Time Frame: 35 months ]
  2. Objective response rate defined as the proportion of patients with a documented complete response and partial response based on RECIST 1.1 [ Time Frame: 35 months ]
  3. Number and severity of adverse events [ Time Frame: 35 months ]
    The incidence of adverse events will be summarized by type of adverse event and severity using the NCI Common Terminology Criteria for Adverse Events. A Fisher's exact test will be used to compare adverse events between the two arms if required



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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 confirmed pancreatic ductal adenocarcinoma which is metastatic.
  • Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
  • Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease with gemcitabine and nab-paclitaxel.
  • Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit within 4 weeks of randomization to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue of adequate amount and quality in order that the specific correlative marker assays proscribed in the protocol may be conducted.
  • Patient must consent to provision of samples of blood, serum and plasma in order that the specific correlative marker assays proscribed may be conducted.
  • Patients must be ≥ 18 years of age.
  • Patients must have an ECOG performance status of 0 or 1 with a life expectancy of at least 12 weeks.
  • No prior treatment for metastatic disease is permitted. Patients may have received prior adjuvant chemotherapy if the last dose was given more than 6 months prior to recurrence. Patients may not have received chemoradiotherapy or adjuvant radiation therapy. Patient may not have received nab-paclitaxel as adjuvant therapy. Prior systemic treatment for borderline resectable or locally advanced disease is not permitted. Patients receiving a single dose of radiation (up to 8Gy/800RAD) with palliative intent for pain control are eligible provided a minimum of 14 days have elapsed between the radiation and the date of randomization.
  • Adequate normal organ and marrow function as defined below (must be done within 14 days prior to registration).

Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥90 g/L Bilirubin ≤ 1.5 x upper normal limit AST and ALT ≤ 2.5 x upper normal limit Serum creatinine <1.25 UNL or Creatinine clearance ≥40mL/min

  • Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 28 days prior to randomization.
  • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
  • Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Patients must agree to return to the participating centre for management of any adverse events which may occur through the course of the trial. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Sites are encouraged to contact CCTG (or their respective Cooperative Group for sites outside Canada) for any questions regarding the interpretation of this criterion. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method

Exclusion Criteria:

  • Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at a low risk of recurrence MAY be eligible. Contact CCTG to discuss eligibility prior to enrolling.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
  • History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression or prior history of severe (grade 3 or 4) immune-mediated toxicity from other immune therapy.
  • Current or prior use of immunosuppressive medication within 28 days before the first planned dose of study therapy, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease) diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangitis), rheumatoid arthritis, hypophysitis, uveitis, etc. within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:

    • Patients with alopecia
    • Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.

NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

  • Patients with active or uncontrolled intercurrent illness including, but not limited to:

    • cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia);
    • active peptic ulcer disease or gastritis;
    • active bleeding diatheses;
    • psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
    • known history of previous clinical diagnosis of tuberculosis;
    • known human immunodeficiency virus infection (positive HIV 1/2 antibodies);
    • known active hepatitis B infection (positive HBV surface antigen (HBsAg)). Patients with a past or resolved HBV infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible;
    • known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal carcinomatosis.
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Receipt of live attenuated vaccination (examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization.
  • Pregnant or lactating women.
  • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
  • Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
  • History of hypersensitivity to gemcitabine, nab-paclitaxel, durvalumab or tremelimumab or any excipient.

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): NCT02879318


Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
The Vitalite Health Network - Dr. Leon Richard
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Kingston Health Sciences Centre
Kingston, Ontario, Canada, K7L 2V7
Grand River Regional Cancer Centre
Kitchener, Ontario, Canada, N2G 1G3
London Regional Cancer Program
London, Ontario, Canada, N6A 5W9
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1H 8L6
Algoma District Cancer Program
Sault Ste. Marie, Ontario, Canada, P6B 0A8
Niagara Health System
St. Catharines, Ontario, Canada, L2S 0A9
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network
Toronto, Ontario, Canada, M5G 2M9
St. Joseph's Health Centre
Toronto, Ontario, Canada, M6R 1B5
Canada, Quebec
Hopital de la Cite-de-la-Sante
Laval, Quebec, Canada, H7M 3L9
L'Hotel-Dieu de Levis
Levis, Quebec, Canada, G6V 3Z1
CHUM-Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2X 3E4
The Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
The Research Institute of the McGill University
Montreal, Quebec, Canada, H4A 3J1
Centre Integre Universitaire De Sante Et De Services
Montreal, Quebec, Canada, H4J 1C5
CHUQ-Pavillon Hotel-Dieu de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
Canadian Cancer Trials Group
AstraZeneca
Investigators
Study Chair: Derek Jonker Ottawa Hospital Research Institute, ON Canada

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02879318     History of Changes
Other Study ID Numbers: PA7
First Posted: August 25, 2016    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Gemcitabine
Tremelimumab
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs