A Phase I/II Study of Intraperitoneal Paclitaxel in Patients With Metastatic Appendiceal Adenocarcinoma
Overview
- Phase
- Phase 1
- Intervention
- Dexamethasone
- Conditions
- Metastatic Appendiceal Adenocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Safety and adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
To find the recommended dose of the drug paclitaxel that can be given intraperitoneally (given directly into the abdominal cavity) to participants with metastatic appendiceal adenocarcinoma.
Detailed Description
Primary (Phase I): 1. To assess the maximum tolerated dose (MTD) of paclitaxel via IP route given every 14 days in subjects with metastatic appendiceal adenocarcinoma Primary (Phase II): 2. To assess the pathologic and radiographic objective response rate of paclitaxel via IP route in participants with metastatic appendiceal adenocarcinoma Secondary Objectives 1. To assess the progression-free and overall survival of metastatic appendiceal adenocarcinoma treated with IP paclitaxel. Although the clinical benefit of this drug has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the participants will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability 2. To assess the pharmacokinetics of IP PTX 3. To assess the change in PCI following IP PTX in patients with metastatic appendiceal adenocarcinoma 4. To assess rate of initially unresectable participants with metastatic appendiceal adenocarcinoma able to undergo CRS / HIPEC after IP PTX 5. To assess the rate of conversion from positive to negative cytology in peritoneal fluid following IP PTX in participants with metastatic appendiceal adenocarcinoma 6. To assess the prognostic value of circulating tumor DNA (ctDNA) in participants with metastatic appendiceal adenocarcinoma and the correlation of quantitative ctDNA measurement with radiographic and pathologic response 7. To generate PDX and PDO models of appendiceal adenocarcinoma and evaluate their ability to predict response of human tumors 8. To evaluate the effect of IP PTX on the transcriptomic state of appendiceal adenocarcinoma and the tumor microenvironment (TME) through comparison of pre- and post-treatment specimens 9. To assess the impact of GNAS, KRAS, TP53, and APC mutation on response to IP PTX therapy 10. To assess the impact of mucinous, signet ring cell, and goblet cell histology on response to IP PTX therapy
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 years and above. There will be no upper age restriction
- •ECOG performance status ≤ 2
- •Participants must have histologically confirmed diagnosis of unresectable locally metastatic appendiceal adenocarcinoma
- •Metastatic disease in the peritoneal cavity and not a candidate for cytoreductive surgery
- •Participants must have adequate organ and marrow function as defined below:
- •leukocytes ≥3000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥75,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) creatinine ≤ 1.5X institutional ULN
- •For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •Participants with metastases outside the peritoneal cavity are not eligible for enrollment
- •Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Exclusion Criteria
- •Active infection such as pneumonia or wound infections that would preclude protocol therapy
- •Participants with unstable angina or New York Heart Association (NYHA) Grade II or greater congestive heart failure
- •Participants deemed unable to comply with study and/or follow-up procedures (i.e., cognitive impairment)
- •Participants with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacity
- •Previous surgery that would preclude safe diagnostic laparoscopy with port placement
- •Participants who have not recovered from adverse events (AE) due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia
- •Participants who are receiving any other investigational agents
- •Participants with metastases outside the peritoneal cavity
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to PTX or other agents used in study
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements Participants who are pregnant
Arms & Interventions
Phase I/Phase II
Participants will be assigned to a study phase (Phase I or Phase II) based on when participants join this study. Up to 4 groups of at least 3 participants will be enrolled in Phase I of the study, and up to 15 participants will be enrolled in Phase II. If you are enrolled in Phase I, the dose of paclitaxel you receive will depend on when the participants join this study. The first group of participants will receive the lowest dose level of paclitaxel. Each new group will receive a higher dose of paclitaxel than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of paclitaxel given intraperitoneally is found. Participants who are enrolled in Phase II, participants will receive paclitaxel at the recommended dose that was found in Phase I.
Intervention: Dexamethasone
Phase I/Phase II
Participants will be assigned to a study phase (Phase I or Phase II) based on when participants join this study. Up to 4 groups of at least 3 participants will be enrolled in Phase I of the study, and up to 15 participants will be enrolled in Phase II. If you are enrolled in Phase I, the dose of paclitaxel you receive will depend on when the participants join this study. The first group of participants will receive the lowest dose level of paclitaxel. Each new group will receive a higher dose of paclitaxel than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of paclitaxel given intraperitoneally is found. Participants who are enrolled in Phase II, participants will receive paclitaxel at the recommended dose that was found in Phase I.
Intervention: Diphenhydramine
Phase I/Phase II
Participants will be assigned to a study phase (Phase I or Phase II) based on when participants join this study. Up to 4 groups of at least 3 participants will be enrolled in Phase I of the study, and up to 15 participants will be enrolled in Phase II. If you are enrolled in Phase I, the dose of paclitaxel you receive will depend on when the participants join this study. The first group of participants will receive the lowest dose level of paclitaxel. Each new group will receive a higher dose of paclitaxel than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of paclitaxel given intraperitoneally is found. Participants who are enrolled in Phase II, participants will receive paclitaxel at the recommended dose that was found in Phase I.
Intervention: Famotidine
Phase I/Phase II
Participants will be assigned to a study phase (Phase I or Phase II) based on when participants join this study. Up to 4 groups of at least 3 participants will be enrolled in Phase I of the study, and up to 15 participants will be enrolled in Phase II. If you are enrolled in Phase I, the dose of paclitaxel you receive will depend on when the participants join this study. The first group of participants will receive the lowest dose level of paclitaxel. Each new group will receive a higher dose of paclitaxel than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of paclitaxel given intraperitoneally is found. Participants who are enrolled in Phase II, participants will receive paclitaxel at the recommended dose that was found in Phase I.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Safety and adverse events (AEs)
Time Frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0