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

NCT02879318 | Completed Phase 2 Results DMC

• 1 other identifier: PA7
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 27

Brief Summary

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

Conditions

Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time from randomization to death from any cause with patients who were alive at the time of the final analysis or who became lost to follow-up censored at their last date known to be alive.

  35 months

Secondary Outcomes (2)

• Progression Free Survival

  35 months

• Objective Response Rate

  35 months

Study Arms (2)

Gemcitabine plus Nab-Paclitaxel

ACTIVE COMPARATOR

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

Drug: Gemcitabine; Drug: Nab-paclitaxel

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab

EXPERIMENTAL

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.

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

Interventions

Gemcitabine DRUG

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab; Gemcitabine plus Nab-Paclitaxel

Nab-paclitaxel DRUG

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab; Gemcitabine plus Nab-Paclitaxel

Durvalumab DRUG

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab

Tremelimumab DRUG

Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (27)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2S 0A9, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

St. Joseph's Health Centre

Toronto, Ontario, M6R 1B5, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

L'Hotel-Dieu de Levis

Lévis, Quebec, G6V 3Z1, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

The Research Institute of the McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Integre Universitaire De Sante Et De Services

Montreal, Quebec, H4J 1C5, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• 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.

  PMID: 36028483 RESULT

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; durvalumab; tremelimumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chris O'Callaghan
• Organization: Canadian Cancer Trials Group

cocallaghan@ctg.queensu.ca

6135336430

Study Officials

• Derek Jonker

  Ottawa Hospital Research Institute, ON Canada

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: August 25, 2016
• Study Start: November 7, 2016
• Primary Completion: August 3, 2020
• Study Completion: March 14, 2025
• Last Updated: March 24, 2025
• Results First Posted: May 28, 2021

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (27)