A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer

Johns Hopkins Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Digestive System Neoplasm; Neoplasm, Glandular; Neoplasms Pancreatic; Pancreatic Diseases; Neoplasms; Endocrine Gland Neoplasms; Digestive System Disease; Adenocarcinoma; Endocrine System Diseases; Pancreatic Neoplasms

Treatments: Drug: Capecitabine; Drug: Gemcitabine; Drug: Cisplatin; Drug: Nab-paclitaxel; Drug: Irinotecan

Study type: Interventional

Funder types: Other

Identifiers

NCT03535727

IRB00167664 (Other Identifier)

J1847

Details and patient eligibility

About

The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with metastatic pancreatic cancer.

Full description

This was a two-part, single-institution, open-label, dose-escalation, phase 1/2 study to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan in patients with metastatic pancreatic cancer.

Part 1 of the study was a Phase 1 3 + 3 dose escalation study designed to evaluate the maximally tolerated dose (MTD) and safety of increasing doses of nab-paclitaxel in combination with gemcitabine, capecitabine, cisplatin, and irinotecan. There were two cohorts of dose escalations. The two cohorts differed based on the treatment cycle length (28 days for Cohort 1 and 21 days for Cohort 2). Dose escalation started with Cohort 1. Enrollment for Cohort 2 dose level 1 began once dose level 2 of Cohort 1 was shown to be safe and did not exceed MTD.

Part 2 was a Phase 2 expansion cohort study for the evaluation of efficacy once the MTD had been determined.

Enrollment: 48 patients

Sex: All

Ages: 18 to 76 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma.
• Patients with the presence of at least one measurable lesion.
• Male or non-pregnant and non-lactating female of age >18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

• Patients who will be considered for surgery are ineligible.
• Patient who have had any prior chemotherapy within 5 years of enrollment.
• Patient who have had radiotherapy for pancreatic cancer.
• Age ≥ 76 years
• Patient who is receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study.
• Patient who has undergone major surgery, other than diagnostic surgery within 28 days prior to Day 1 of treatment in this study.
• Patient who has known brain metastases.
• Patient with history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, nab-paclitaxel, capecitabine, cisplatin, or irinotecan.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient who has serious medical risk factors involving any of the major organ systems.
• Patient who has known history of infection with HIV, hepatitis B, or hepatitis C.
• Pregnant or breast feeding.
• Patient is unwilling or unable to comply with study procedures
• Patient with clinically significant wound.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

48 participants in 9 patient groups

Phase 1, Cohort 1, Dose level 1

Experimental group

Description:

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel: 40 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 1, Dose level 2

Experimental group

Description:

Gemcitabine 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel 60 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 1, Dose level 3

Experimental group

Description:

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel: 80 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan:20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 1, Dose level 4

Experimental group

Description:

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:100 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan:20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 1, Dose level 5

Experimental group

Description:

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 2, Dose level 1

Experimental group

Description:

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:40 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 2, Dose level 2

Experimental group

Description:

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:60 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 1, Cohort 2, Dose level 3

Experimental group

Description:

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Nab-paclitaxel:80 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine

Phase 2 Dose Expansion (Cohort 1, DL5)

Experimental group

Description:

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Nab-paclitaxel:125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Irinotecan

Drug: Nab-paclitaxel

Drug: Cisplatin

Drug: Gemcitabine

Drug: Cisplatin

Drug: Capecitabine