Clinical trial NCT04605913: Nab-Paclitaxel + Cisplatin + Gemcitabine + TTF in pt. w/ Metastatic PAC
Official title: A Phase I/Ib Pilot Trial, Single Arm, Open Label, of Protein-Bound Paclitaxel, Cisplatin, and Gemcitabine (GCN) Combined With Tumor Treatment Fields (TTF) in Patient With Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreas Cancer
Metastatic Pancreatic Cancer
Pancreatic Adenocarcinoma
Metastatic Adenocarcinoma
Keywords: GCN
TTF
Paclitaxel
Cisplatin
Gemcitabine
Tumor Treatment Fields
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: NovoCure Ltd.
First posted: 2020-10-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The trial will compose of 2 parts with a total of 40 subjects. The 1st part would be a safety run-in phase (phase I). In this phase, 6 patients will be treated after completing screening procedures and meeting eligibility criteria. If 6 patients tolerate this dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).
Primary purpose: TREATMENT

Brief summary: This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with Tumor Treatment Fields (TTF) and G+TTF maintenance therapy in patients with metastatic pancreatic cancer.

Detailed description: GCN is predicted to be the front-line therapy for biliary and pancreatic cancer in the future given excellent results of current early clinical trials (ORR ≥ 67% in pancreatic cancer). This will change standard of care for front-line therapy in patients with stage IV pancreatic cancer. In this cohort of patients' tolerability after 6 cycles of therapy will be a challenge. Investigators hypothesize that developing a maintenance strategy with TTF+G will be cutting edge approach and can potentially transform front-line standard of care therapy in patients with stage IV pancreatic cancer. If this pilot study proves fruitful then a larger study to confirm findings can be conducted.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed pancreatic adenocarcinoma or adeno-squamous carcinoma with liver metastasis.

   1. Subjects with additional sites of metastasis, except known brain metastasis, are eligible.
   2. Histologies excluded include squamous, small cell carcinoma, and acinar cell carcinoma. However, adeno-squamous histology can be enrolled.
   3. Patients who have recurrence or metastasis after surgery and adjuvant therapy do not need repeat biopsy for confirmation of recurrence if clinical suspicion is high per scans (MRI/CT scan), with and without CA 19-9 elevation, specifically if biopsy is unsafe or technically difficult.
2. Patients with no prior lines of therapy for the treatment of stage IV metastatic disease.

   1. Patients could have had prior neoadjuvant or adjuvant chemotherapy or chemo-radiotherapy.

   i. Patients who received gemcitabine-based adjuvant chemotherapy can enroll if they progress greater than 6 months after completion of the therapy; ii. Patients who progress while on adjuvant FOLFIRINOX can enroll immediately.
3. Male and female patients at least 18 years of age
4. Laboratory data as specified below:

   Hematology:

   - ANC greater than 1500 cells/mm3,

   - platelet count greater than 100,000 cells/mm3, and

   - Hemoglobin greater than 8 g/dL.
   * Hepatic

     * Total bilirubin less than 1.5 X ULN;
     * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 3 X ULN.

   For patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 6.0 X ULN and total bilirubin less than 3 x ULN.
   * Renal:

     * serum creatinine WNL or creatinine clearance greater than 50 mL/min.
5. QT intervals: QTc less than or equal to 470 msec for men and less than or equal to 490 msec for women. (As measured by Hodges' Equation: QTc = QT + 1.75(rate-60) where QTc = corrected QT interval and rate = ventricular rate/min).
6. Estimated life expectancy of at least 3 months
7. ECOG Performance Status 0-1.
8. Ability to operate the Novo TTF-100L (P) system.
9. Patients must have measurable disease on scans per RECIST 1.1.
10. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of study treatment.

Exclusion Criteria:

1. Previous front-line therapy for metastatic disease.

1. Patients with known brain metastasis.
2. Cardiac conduction abnormalities such as 2nd and 3rd heart-block requiring a pacemaker.
3. Patient with cardiac or abdominal pacemakers or stimulators.
4. Significant risk of cardiac drug toxicity due to congestive heart failure or history of myocardial infarction.
5. Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible.
6. Concomitant use of drugs that have black box warning of Torsades de Pointes will also be prohibited if cannot be replaced by another drug.
7. Known sensitivity to conductive hydrogels.

10. Patients who are pregnant or breastfeeding.

Primary outcomes:
measure: Safety of (m)-GCN+TTF
timeFrame: 28 days
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Six months
measure: Overall Response Rate (ORR)
timeFrame: Six months
measure: Overall Survival (OS)
timeFrame: Twelve months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Hani M. Babiker, MD
role: PRINCIPAL_INVESTIGATOR
References: