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Gemcitabine Versus Reduced-dose Combination Chemotherapy in Fragile Patients With Non-resectable 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05841420
Recruitment Status : Recruiting
First Posted : May 3, 2023
Last Update Posted : July 27, 2023
Sponsor:
Collaborators:
Aarhus University Hospital
Odense University Hospital
Herlev and Gentofte Hospital
Gødstrup Hospital
Vejle Hospital
Information provided by (Responsible Party):
Morten Ladekarl, Aalborg University Hospital

Tracking Information
First Submitted Date  ICMJE March 16, 2023
First Posted Date  ICMJE May 3, 2023
Last Update Posted Date July 27, 2023
Actual Study Start Date  ICMJE June 12, 2023
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2023)
PFS (Progression Free Survival) [ Time Frame: 1 year from end of study accrual. ]
PFS is defined in the ITT population as the date of the randomization to the date of disease progression or date of death, whichever comes first. The date of PD is the date of scan, if progression is found on a CT scan, or date of visit at which clinical progression is found. PD at CT is defined according to RECIST version 1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2023)
  • OS (Overall Survival) [ Time Frame: 1 year from end of study accrual. ]
    OS is defined in the ITT population as the date of randomization to date of death of all causes.
  • RR (Response rate) [ Time Frame: 1 year from end of study accrual. ]
    In patients with measurable disease at baseline, RECIST version 1.1 will be used for evaluation of complete response (CR), partial response (PR), stable disease (SD) or PD. ORR will be calculated as the percentage of patients with CR+PR of all patients with measurable disease, who received at least one treatment and were evaluated by at least one diagnostic CT scan.
  • Hospitalizations [ Time Frame: Through study completion, an average of 6 months. ]
    The total number of hospital admissions in a stationary unit with overnight stay from the start of treatment to the date of end of treatment will be assessed in the treated population. If the patient is readmitted for the same reason within 3 days (e.g., after weekend leave), this is not counted as a separate admission. The reasons for admission are registered as toxicity due to treatment or symptoms due to PC. The sum of hospitalizations is calculated for each randomization arm for comparison.
  • Quality of Life (QOL) assessed by EORTC QLQ-C30 at baseline and after 8, 16, and 24weeks [ Time Frame: At baseline and at 8, 16, and 24 weeks. ]
    QoL scores collected will be linearly transformed to a scale of 0 to 100. Items will be grouped in health status scale (range 0 - 100, high is better), functional scales (range 0 - 100, high is better) and symptom scales (range 0 - 100, low is better). Each scale is summarized by its mean, and standard deviation for the patients in the two treatment groups. The difference in mean at 8, 16 and 24 weeks are compared with the baseline mean within in each treatment groups. The difference in mean between the treatment groups are compared at baseline, 8, 16 and 12 weeks.
  • Cumulative worst toxicity during treatment [ Time Frame: From date of first treatment until 1 year from end of study treatment. ]
    (Adverse events ≥ grade 3 according to CTCAE version 5.0). All patients who have received 1 dose of chemotherapy will be calculated in the safety analyses. Cumulative worst toxicities ≥CTC grade 3 in the treated population are registered for each arm separately for comparison.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine Versus Reduced-dose Combination Chemotherapy in Fragile Patients With Non-resectable Pancreatic Cancer
Official Title  ICMJE A Randomized Phase II Study of Gemcitabine Versus Reduced-dose Combination Chemotherapy in Fragile Patients With Non-resectable Pancreatic Cancer
Brief Summary

The aim of the study is to compare the efficacy and toxicity of full-dose Gemcitabine and reduced-dose combination chemotherapy in patients with non-resectable pancreatic cancer, who are unfit for full-dose combination chemotherapy.

The patients will be equally randomized to arm A or arm B:

Arm A: Full-dose single agent treatment with Gemcitabine 1000 mg/m2 weekly on days 1, 8,and 15 every 4 weeks.

Arm B: Reduced-dose (80%) combination-treatment with Gemcitabine plus Nab-Paclitaxel (Gemcitabine: 800 mg/m2 plus Nab-Paclitaxel: 100 mg/m2 on day 1, 8 and 15 every 4 weeks)

Progression-free survival, overall survival and response rate will be estimated for each group, as well as toxicity and quality of life will be prospectively registered.

Detailed Description

According to guidelines the recommended treatment for patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas old and/or fragile patients can be offered Gemcitabine monotherapy, if they are fit for treatment. Phase III trials show improved effect of combination chemotherapy compared to Gemcitabine, but these trials were restricted to fit patients younger than 75 years of age, as full-dose combination chemotherapy is more toxic.

Studies in colorectal cancer and a post-hoc analysis of Gemcitabine plus Nab-Paclitaxel in PC suggest that reduced-dose of combination chemotherapy may be more efficient in terms of progression-free survival and less toxic as compared to monotherapy in elderly and/or frail patients, but reduced start-dosing of GemNab is not currently labelled.

Moreover, a recent Danish register-based study showed that more use of combination chemotherapy at oncological departments was associated with improved outcome of patients with PC.

Elderly and frail patients with PC are in great need of better treatment results. Hence, a comparative study of reduced-dose combination chemotherapy is warranted and may be practice changing.

The aim of the study is to compare the efficacy and toxicity of full-dose Gemcitabine and reduced-dose combination chemotherapy in patients with non-resectable PC, who are unfit for full-dose combination chemotherapy.

The study is a national multicenter prospective randomized phase II trial, endorsed by the Danish Pancreas Cancer Group (DPCG). 98 patients with non-resectable PC, unfit for full-dose combination chemotherapy, but eligible for first-line chemotherapy, will be included.

The patients will be equally randomized to arm A or arm B:

Arm A: Full-dose single agent treatment with Gemcitabine 1000 mg/m2 weekly on days 1, 8 and 15 every 4 weeks.

Arm B: Reduced-dose (80%) combination-treatment with GemNab (Gemcitabine: 800 mg/m2 plus Nab-Paclitaxel: 100 mg/m2 on day 1, 8 and 15 every 4 weeks).

Progression-free survival, overall survival and response rate will be estimated for each group, as well as toxicity and quality of life will be prospectively registered.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreas Cancer
  • Non-Resectable Pancreas Carcinoma
Intervention  ICMJE
  • Drug: Gemcitabine
    Gemcitabine monotherapy, 1000 mg/m2 weekly on days 1, 8, and 15 every 4 weeks or gemcitabine: 800 mg/m2 on day 1, 8 and 15 every 4 weeks
    Other Name: Gemzar
  • Drug: Nab paclitaxel
    Nab-Paclitaxel: 100mg/m2 on day 1, 8 and 15 every 4 weeks
    Other Name: Abraxane
Study Arms  ICMJE
  • Active Comparator: A: "Full dose single agent strategy"
    Gemcitabine monotherapy, 1000 mg/m2 weekly on days 1, 8, and 15 every 4 weeks
    Intervention: Drug: Gemcitabine
  • Experimental: B: "Reduced dose (80%) combination-therapy strategy"
    Nab-Paclitaxel: 100mg/m2 plus gemcitabine: 800 mg/m2 on day 1, 8 and 15 every 4 weeks
    Interventions:
    • Drug: Gemcitabine
    • Drug: Nab paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 1, 2023)
98
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2025
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years
  • Adenocarcinoma of the pancreas, histopathologically or cytologically verified
  • Non-resectable (locally advanced or metastatic) PC
  • Patients unfit or not candidate for full-dose combination chemotherapy
  • Patients eligible for full dose gemcitabine or reduced dose combination chemotherapy
  • Performance status (PS) ≤2
  • Measurable or non-measurable disease
  • Adequate hematologic function defined as absolute neutrophil count (ANC) ≥1.5 x 10^9/l and platelets count ≥100x10^9/l within 2 weeks prior to enrollment
  • Adequate organ function (bilirubin ≤1.5 x UNL (Upper Normal Limit) and eGFR (estimated Glomerular Filtration Rate) >50ml/min within 2 weeks prior to enrollment
  • Toxicity of prior chemotherapy, including neurotoxicity, resolved to CTCAE <grade 2
  • Oral and written informed consent must be obtained according to the local Ethics committee requirements
  • Fertile patients must use adequate contraceptives

Exclusion Criteria:

  • Patients eligible for downstaging/preoperative chemotherapy followed by resection or local ablation or irradiation
  • Prior chemotherapy for PC (However, patients treated with adjuvant therapy with recurrence occurring more than 6 months after end of this treatment are eligible)
  • Concurrent, non-curatively treated malignant neoplasm other than pancreatic adenocarcinoma
  • Concurrent treatment with any other anti-cancer therapy
  • Pregnant or breast-feeding patients
  • Patients clearly intending to withdraw from the study if not randomized in the willing arm or patients who cannot be regularly followed up for psychological, social, familiar, or geographic reasons.
  • Other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
  • Known allergy or intolerance to any of the drugs used in DPCG-01 (Gemcitabine, S1 or Nab-Paclitaxel)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Morten Ladekarl, Professor 0045+61399326 morten.ladekarl@rn.dk
Contact: Louise Rasmussen, PhD 0045+30226432 loskr@rn.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05841420
Other Study ID Numbers  ICMJE DPCG-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Morten Ladekarl, Aalborg University Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Morten Ladekarl
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Aarhus University Hospital
  • Odense University Hospital
  • Herlev and Gentofte Hospital
  • Gødstrup Hospital
  • Vejle Hospital
Investigators  ICMJE
Principal Investigator: Morten Ladekarl, Professor Aalborg Universitets Hospital, Department of Oncology
PRS Account Aalborg University Hospital
Verification Date July 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP