Trial Title:
A Phase 1b Study of Gemcitabine and Nab-paclitaxel in Combination With IM156 in Patients With Advanced Pancreatic Cancer.
NCT ID:
NCT05497778
Condition:
Pancreas Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Given by IV (vein)
Arm group label:
Dose Escalation Phase followed by a Dose Expansion Phase
Other name:
Gemcitabine Hydrochloride
Other name:
Gemzar®
Intervention type:
Drug
Intervention name:
Nab paclitaxel
Description:
Given by IV (vein)
Arm group label:
Dose Escalation Phase followed by a Dose Expansion Phase
Other name:
Paclitaxel (protein-bound)
Other name:
Abraxane, ABI-007
Intervention type:
Drug
Intervention name:
IM156
Description:
Given by PO
Arm group label:
Dose Escalation Phase followed by a Dose Expansion Phase
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.
Detailed description:
Primary Safety Objective:
To evaluate the safety and tolerability of IM156 with Gem+NP in patients with metastatic
PDAC
Exploratory Efficacy Objective:
To evaluate the efficacy of IM156 with Gem+NP in patients with metastatic PDAC
Exploratory Biomarker Objective:
To identify biomarkers that are predictive of response to IM156 (i.e., predictive
biomarkers), are associated with progression to a more severe disease state (i.e.,
prognostic biomarkers), are associated with resistance to IM156, are associated with
susceptibility to developing adverse events, can provide evidence of study treatment
activity, or can increase the knowledge and understanding of disease biology.
Criteria for eligibility:
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
- Total bilirubin ≤ 1.5 x upper limit of normal (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. Patients who have undergone CNS directed treatment can be enrolled
provided they show evidence of stable lesions (and no new lesions) with no evidence
of tumor progression for at least 4 weeks after CNS-directed treatment. Patients do
not require a baseline imaging, unless clinically indicated.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shubham Pant, MD
Phone:
832-803-5306
Email:
spant@mdanderson.org
Investigator:
Last name:
Shubham Pant, MD
Email:
Principal Investigator
Start date:
October 21, 2022
Completion date:
January 8, 2025
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05497778
http://www.mdanderson.org
