Overview

A Phase 1b Study of Gemcitabine and Nab-paclitaxel in Combination With IM156 in Patients With Advanced Pancreatic Cancer.

Status:
Not yet recruiting
Trial end date:
2025-01-08
Target enrollment:
0
Participant gender:
All
Summary
To learn if adding a new medication, IM156, to treatment with gemcitabine and nab-paclitaxel is safe and tolerable. The ability of this combination to improve the success of this treatment for these patients will also be studied.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Albumin-Bound Paclitaxel
Gemcitabine
Paclitaxel
Criteria
Inclusion Criteria:

For inclusion in the study patients must fulfill all the following criteria:

- Ability to understand and the willingness to sign a written informed consent form
(ICF).

- Male or female participants ≥ 18 years of age at the time of screening. Because no
dosing or adverse event data are currently available on the use of IM156 in
combination with Gem + NP in patients <18 years of age, children are excluded from
this study.

- Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma.

- Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
1.1 criteria [13], defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded for non-nodal lesions and
short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm)
with CT scan, MRI, or calipers by clinical exam. The measurable lesion must be outside
of a radiation field if the participant received prior radiation.

- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (see
Appendix 1).

- Naïve to any prior treatment for metastatic disease, including chemotherapy,
biological therapy, or targeted therapy.

- Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for
pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was
completed at least 6 months prior to study enrollment. Prior adjuvant therapy may
include Gem or NP.

- Participants initially diagnosed with localized pancreatic cancer who have
undergone chemotherapy then resection and had no evidence of disease are eligible
if relapse of metastatic disease has occurred and if the last dose of
chemotherapy was received more than 6 months before study entry.

- Prior radiation therapy must have been completed at least 14 days before
investigational product administration.

- Prior surgery that required general anesthesia or other major surgery as defined by
the investigator must be completed at least 4 weeks before investigational product
administration.

- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial.

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable viral load

- Men treated or enrolled on this protocol must also agree to use adequate contraception
prior to the study (hormonal or barrier method of birth control; abstinence), for the
duration of study participation, and 90 days after completion of IM156 administration.

- The effects of IM156 on the developing human fetus are unknown. For this reason, all
women of child-bearing potential (refer to MDA Policy CLN 1114), which includes all
female patients younger than 55 years, must meet one of the following inclusion
criteria:

- Postmenopausal (no menses in greater than or equal to 12 consecutive months)

- History of hysterectomy or bilateral salpingo-oophorectomy.

- Ovarian failure (follicle stimulating hormone and estradiol in menopausal range,
who have received whole pelvic radiation therapy)

- History of bilateral tubal ligation or another surgical sterilization procedure.)

- Use of approved methods of birth control before the study, for the duration of
study participation, 90 days after completion of IM156 administration, and for at
least 6 months after the final dose of NP. Approved methods are as follows:
Hormonal contraception (i.e. birth control pills, injection, implant, transdermal
patch, vaginal ring), Intrauterine device (IUD), tubal ligation or hysterectomy,
patient/partner post vasectomy, implantable or injectable contraceptives, and
condoms plus spermicide. Not engaging in sexual activity for the total duration
of the trial and the drug washout period is an acceptable practice; however
periodic abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of birth control. For all women of childbearing potential who
do not meet one of the four criteria above, a negative serum pregnancy test will
be required within 2 weeks prior to dosing.

- Patients 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.

- Patients must have adequate organ and marrow function as defined below:

- Absolute neutrophil count ≥1,000/mcL (in absence of growth factor support)

- Platelets ≥100,000/mcL

- Hemoglobin ≥ 9.0 g/dl

- Aspartate aminotransferase (AST) ≤ 2.5 x ULN without hepatic metastasis and ≤ 5 x
ULN with hepatic metastasis

- Alanine aminotransferase (ALT) ≤ 2.5 x ULN without hepatic metastasis and ≤ 5 x
ULN with hepatic metastasis

- Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) (except participants with
Gilbert's syndrome who must have direct bilirubin ≤ 3.0 mg/dL).
AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

- Creatine clearance >50 as calculated by the Cockcroft Gault Formula

- Patients with new brain metastases (active brain metastases) or leptomeningeal disease
are eligible if the treating physician determines that immediate CNS specific
treatment is not required and is unlikely to be required during the first cycle of
therapy.

Exclusion Criteria:

- Patients with a current evidence of diabetes mellitus who are currently being treated
with another biguanide (e.g., metformin)

- Patients who are currently being treated with the following medications, which are
sensitive CYP2D6 substrates per FDA.gov (Drug Development and Interactions; Table of
Substrates, Inhibitors, and Inducers): atomoxetine, desipramine, dextromethorphan ,
eliglustat(e), nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine

- Patients with a history of serious gastrointestinal bleeding within 6 weeks prior to
screening or patients with any disease possibly affecting the absorption of oral
agents (malabsorption syndrome, hemorrhagic gastric ulcer, etc.)

- Patients with suspected serious infectious diseases, intestinal paralysis, bowel
obstruction, interstitial pneumonia, or pulmonary fibrosis.

- Patients with a history of alcohol or drug abuse within 12 weeks prior to screening

- The effects of IM156 on the developing human fetus are unknown. For this reason, women
who are pregnant or breastfeeding are excluding from this study. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in this
study, she should inform her treating physician immediately.

- Patients with uncontrolled underlying medical conditions (e.g., interstitial lung
disease, active infections requiring antibiotics, recent hospitalization with
unresolved symptoms, symptomatic congestive heart failure [New York Heart Association
class III or IV], unstable angina, uncontrolled hypertension, cardiac arrhythmia,
interstitial lung disease, active coagulopathy).

- Patients with psychiatric illness/social situations that would limit compliance with
study requirements.

- History of myocardial infarction within 6 months or history of arterial thromboembolic
event within 3 months of the first dose of investigational agent.

- Any active autoimmune disease.

- Any concurrent investigational anticancer therapy.

- Any concurrent immunosuppressive medications, including chronic systemic
corticosteroids at greater than physiologic doses (a dose of 10 mg/day oral prednisone
or equivalent) 14 days before the first dose (except for participants who require
hormone replacement therapy such as hydrocortisone). A temporary course (≤ 3 days) of
corticosteroids (i.e., contrast allergy, chronic obstructive pulmonary disease) may be
permitted, depending on the duration and dose, after discussion and agreement with the
PI.

- Any concurrent chemotherapy, radiotherapy (except palliative radiotherapy),
immunotherapy, biologic, or hormonal treatment. Concurrent use of hormones for
noncancer-related conditions is permitted.

- Patients who have not recovered from adverse events due to prior anticancer therapy
(i.e., have residual toxicities > Grade 1) except for alopecia.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to IM156, Gem or NP.