Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis

Summary

Background:

Tumors that have spread to the lining of the abdomen from other cancers, such as cancer of the appendix, colon, or ovary, are called peritoneal carcinomatosis. In most cases, outcomes are poor. Researchers want to test a new treatment.

Objective:

To learn if the combination of oral nilotinib plus paclitaxel given by intravenous (IV) and directly into the abdomen can reduce tumors enough for people to have surgery.

Eligibility:

Adults aged 18 and older with peritoneal carcinomatosis that is too widespread for surgery.

Design:

Participants will be screened with:

Physical exam

Medical history

Blood and urine tests

Electrocardiogram

Laparoscopy. They will get general anesthesia. Small cuts will be made in their abdomen. Tissue and fluid samples will be taken.

Surveys about their health

Computed tomography (CT) scans of their torso

Participants will have up to 4 more laparoscopies. During the first procedure, a port will be placed under the skin of their abdomen (an intraperitoneal (IP) port). It will be attached to a catheter that is placed in their abdomen.

Participants will get treatment in 3-week cycles, for 3 or 6 cycles. They will take nilotinib by mouth twice daily. They will get paclitaxel by IP port (once per cycle) and by IV (twice per cycle). After cycles 3 and 6, they will have a laparoscopy and CT scans. Then they may take nilotinib and get IV paclitaxel for up to 1 year.

At study visits, participants will repeat some screening tests.

About 6 weeks after treatment ends and then every 3 months for 3 years, participants will have follow-up visits at National Institutes of Health (NIH) or with their local doctor.

Conditions

• Gynecologic Cancer
• Gynecologic Neoplasms
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Colorectal Cancer
• Colorectal Neoplasms
• Appendiceal Cancer
• Appendiceal Neoplasms
• Cholangiocarcinoma
• Breast Cancer

Interventions

DRUG

Paclitaxel

Paclitaxel: Intraperitoneal (IP) paclitaxel will be dosed at 60 mg/m\^2 to be infused over 1 hour on Day 1 of each 3-week cycle; participants with unresectable, but stable or responding disease after C1 through C3 will dose increase IP paclitaxel to 80 mg/m2 for Cycles 4-6. Intravenous (IV) paclitaxel will be infused over 1 hour on Day 2 of the first week of Cycle 1, followed by Day 1 of the subsequent treatment weeks; IV paclitaxel will be dosed at 60 mg/m2 for Week 1 of Cycle 1 and, if tolerated, at 80 mg/m2 for subsequent treatments.

DRUG

Nilotinib

Oral nilotinib will be dosed at 300 mg twice daily. Nilotinib will be administered continually from the loading dose (Day -4) leading up to laparoscopy #2 onward.

DIAGNOSTIC_TEST

ECG

Screening, Week -1, Cycle 1 and 4 Day 1 (±3 days at start of cycle), Cycle 2 and 5 Day 1 (±3 days at start of cycle), Cycle 3 and 6 Day 1 (±3 days at start of cycle) and 4-8 Weeks post-therapy (±2 weeks).

DIAGNOSTIC_TEST

CT Scan CAP

Screening, Cycle 3 and 6 Day 1, Week 6, and every 3 months (± 2 weeks) for up to 3 years total.

PROCEDURE

Laparoscopy

Screening, Day 0, Week -1, and Cycle 3 and 6, Week 3.

PROCEDURE

Peritoneal biopsies + ascites washings

Screening (intra-op), Week -1, Day 0 (intra-op), and on treatment (± 1 day), Cycle 3 and 6, Week 3 (intra-op). Biopsy only done if deemed eligible per laparoscopy (only performed during laparoscopy).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Andrew M Blakely, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-10-13

Primary Completion

2025-01-27

Completion

2025-01-27

FDA Drug

Yes

Countries

• United States

Study Locations