RACING (RAmucirumab Combined wIth standard Nab-paclitaxel and Gemcitabine as first-line chemotherapy in patients with advanced pancreatic adenocarcinoma) trial is a Greek, investigator-initiated, single-arm, open-label phase Ib-II study. Patients with advanced cytologically or histologically proven pancreatic adenocarcinoma will be treated with a combination of Ramucirumab with Nab-paclitaxel and Gemcitabine (for a maximum of 8 cycles followed by Ramucirumab maintenance) until disease progression or excessive Adverse Events (AEs) or Investigator's decision or patient's refusal of further treatment or death, whichever comes first.
Phase Ib: The first 12 patients will enter the phase Ib study in 2 cohorts of 6 patients each. In the first cohort, six patients will start Ramucirumab followed by Nab-paclitaxel and Gemcitabine every 4 weeks for 2 cycles at the specific initial dose level.When the dose is determined in the first cohort, then the second cohort will be enrolled to test the safety of this dose. The Phase II Recommended dose (RD) for the phase II part of the study will be determined when all 6+6 patients will complete a maximum of 2 cycles. Phase II: In the phase II part of the trial, new patients will be recruited and start the study treatment according to the RD determined at the second cohort of the phase Ib part. Phase Ib patients will enter the phase II part by continuing the treatment beyond the second cycle at the RD level. All the patients will continue the treatment until disease progression or excessive AEs or completion of 8 cycles of Nab-paclitaxel/Gemcitabine/Ramucirumab. In patients with no progressive disease, ramucirumab monotherapy will be administered after the completion of 8 cycles of chemotherapy. The primary endpoint will be Objective Response Rate (ORR) by RECIST criteria. Secondary endpoints will be Safety, Progression-free survival (PFS) and Overall Survival (OS). All the phase II endpoints will be assessed during BOTH the phase Ib and the phase II parts of the study. Patients enrolled at the phase Ib part will start being assessed for efficacy endpoints (response rate, PFS, OS) from the first date of registration to the study and will continue being assessed for efficacy also after passing to the phase II part of the study in a seamless way. After completion of patient enrollment in the phase Ib part, new patients will be enrolled directly to the phase II part. These patients will start being assessed for efficacy endpoints again from the first day of registration to the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
8 mg/kg (days 1 and 15, q4w) until disease progression
Agios Savvas Anticancer Hospital
Athens, Attica, Greece
Aretaieio Hospital
Athens, Attica, Greece
"Attikon" University Hospital
Chaïdári, Attica, Greece
Metropolitan General Hospital
Cholargós, Attica, Greece
Metropolitan Hospital
Neo Faliro, Attica, Greece
Ygeia Hospital
Psychikó, Attica, Greece
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital
Athens, Nea Kifisia, Greece
Agii Anargiri Cancer Hospital
Athens, Nea Kifisia, Greece
University Hospital of Patra
Rio, Patra, Greece
EUROMEDICA General Clinic of Thessaloniki
Thessaloniki, Thessaloniki, Greece
...and 3 more locations
Phase Ib: Assessment of safety by identifying the Recommended Dose (RD) of the combination of Ramucirumab with Nabpaclitaxel and Gemcitabine.
Time frame: From enrollment up to 90 days after the last administration of any investigational product
Phase II: Overall Response Rate is defined as the proportion of patients with confirmed Complete Response or confirmed Partial Response as best overall response to treatment, based on RECIST v. 1.1 guidelines in the considered analysis population.
Time frame: Up to 33 months
Overall survival (OS)
Time frame: Up to 33 months
Progression-free survival
Time frame: Every 8 weeks until month 8 and then every 12 weeks, up to 33 months
Phase I:Toxicity profile of the combination during the first 2 cycles of therapy
Time frame: From the first administration of study treatment and up to week 8 (during the first 2 cycles of the treatment, each cycle is 28 days)
Phase II: Number of participants with Serious and Non-Serious Adverse Events graded according to National Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Time frame: From enrollment up to 33 months.
Investigation of SPARC gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of PTEN gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of MEK gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of AREG gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of EREG gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of VEGF-A gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of VEGF-B gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of PlGF gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of TSP1 gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of MMP2 gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of MMP9 gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
Investigation of VEGFR1-3 gene mutation, m-RNA and protein expression
Time frame: At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months
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