Clinical trial NCT05841420: Gemcitabine Versus Reduced-dose Combination Chemotherapy in Fragile Patients with Non-resectable Pancreatic Cancer
Official title: A Randomized Phase II Study of Gemcitabine Versus Reduced-dose Combination Chemotherapy in Fragile Patients with Non-resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreas Cancer
Non-Resectable Pancreas Carcinoma
Keywords: Fragile
Elderly
Palliative
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Odense University Hospital
name: Herlev and Gentofte Hospital
name: Gødstrup Hospital
name: Vejle Hospital
First posted: 2023-05-03
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: PFS (Progression Free Survival)
timeFrame: 1 year from end of study accrual.
Secondary outcomes:
measure: OS (Overall Survival)
timeFrame: 1 year from end of study accrual.
measure: RR (Response rate)
timeFrame: 1 year from end of study accrual.
measure: Hospitalizations
timeFrame: Through study completion, an average of 6 months.
measure: Quality of Life (QOL) assessed by EORTC QLQ-C30 at baseline and after 8, 16, and 24weeks
timeFrame: At baseline and at 8, 16, and 24 weeks.
measure: Cumulative worst toxicity during treatment
timeFrame: From date of first treatment until 1 year from end of study treatment.
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Oncology, Aalborg University Hospital
Study officials:
affiliation: Aalborg Universitets Hospital, Department of Oncology
name: Morten Ladekarl, Professor
role: PRINCIPAL_INVESTIGATOR
References: