Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma

NCT ID: NCT02879318

Last Updated: 2025-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-07
• Study Completion Date: 2025-03-14

Brief Summary

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

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.

Conditions

Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine plus Nab-Paclitaxel

Gemcitabine 1000 mg/m2 IV \& Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days.

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Nab-paclitaxel

Intervention Type: DRUG

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab

Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Nab-paclitaxel

Intervention Type: DRUG

Durvalumab

Intervention Type: DRUG

Tremelimumab

Intervention Type: DRUG

Interventions

Gemcitabine

Intervention Type: DRUG

Nab-paclitaxel

Intervention Type: DRUG

Durvalumab

Intervention Type: DRUG

Tremelimumab

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek Jonker

Role: STUDY_CHAIR

Ottawa Hospital Research Institute, ON Canada

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

St. Joseph's Health Centre

Toronto, Ontario, Canada

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

L'Hotel-Dieu de Levis

Lévis, Quebec, Canada

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

The Jewish General Hospital

Montreal, Quebec, Canada

The Research Institute of the McGill University

Montreal, Quebec, Canada

Centre Integre Universitaire De Sante Et De Services

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Renouf DJ, Loree JM, Knox JJ, Topham JT, Kavan P, Jonker D, Welch S, Couture F, Lemay F, Tehfe M, Harb M, Aucoin N, Ko YJ, Tang PA, Ramjeesingh R, Meyers BM, Kim CA, Du P, Jia S, Schaeffer DF, Gill S, Tu D, O'Callaghan CJ. The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma. Nat Commun. 2022 Aug 26;13(1):5020. doi: 10.1038/s41467-022-32591-8.

Reference Type: RESULT

PMID: 36028483 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PA7

Identifier Type: -

Identifier Source: org_study_id