Clinical trial NCT05868226: PRE-I-SPY Phase I/Ib Oncology Platform Program
Official title: PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/Ib Platform Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HER2-positive Breast Cancer
Metastatic Cancer
Metastatic Breast Cancer
Metastatic
HER2-positive Metastatic Breast Cancer
HER2 Mutation-Related Tumors
HER-2 Protein Overexpression
HER2-negative Breast Cancer
Triple Negative Breast Cancer
HR Positive
Hormone Receptor-positive Breast Cancer
Estrogen Receptor Positive Tumor
Progesterone Receptor-positive Breast Cancer
Hormone Receptor Negative Breast Carcinoma
Solid Tumor
Solid Tumor, Adult
Solid Carcinoma
HER2 Low Breast Cancer
HER2 Low Breast Carcinoma
ER Positive Breast Cancer
PR-positive Breast Cancer
Keywords: I-SPY Trials
Quantum Leap Healthcare Collaborative
QLHC
I-SPY
I-SPY2
I-SPY1
PRE-ISPY
PRE-I-SPY
I-SPY Phase 1
I-SPY Phase 1b
I-SPY-P1
ISPY
ISPYP1
I-SPY Phase 1 Platform
ISPY2
ISPY1
Phase 1 Platform
Phase 1 Oncology Platform
T-DXd naive
PRE1
PRE2
PRE3
PRE
PRE-I-SPY Phase 1
PRE-I-SPY Phase 1b
ALX148
T-DXd
Enhertu
Zanidatamab
Tucatinib
Ziihera
Tukysa
Evorpacept
QL
Lead sponsor: QuantumLeap Healthcare Collaborative
Sponsor class: OTHER
First posted: 2023-05-22
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, multi-site, multi-arm platform study, where each drug regimen arm may have different study designs and eligibility. In particular, dose finding parts may employ different designs (e.g., 3+3, Bayesian Optimal Interval Design \[BOIN\], continual reassessment method \[CRM\], etc.) for each arm in the PRE-I-SPY program. See each arm for specific study model details.
Primary purpose: TREATMENT

Brief summary: I-SPY Phase I/Ib (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials in a timely manner.

Detailed description: The PRE-I-SPY/I-SPY-P1 study is a platform trial with multiple ongoing drug regimen arms. In most cases, the treatment arm will have a dose-finding group (Part 1) and a dose-expansion group (Part 2). Eligibility criteria will vary according to the experimental regimen. Participant eligibility may vary according to the arm or the part within the study arm, including with respect to diagnosis. Arms could include participants diagnosed with certain solid tumors or specifically with breast cancer. Arms may restrict enrollment to a certain molecular pathway abnormality or histologic diagnosis. The trial allows for various study arm designs, with the goal to complete analysis of a study arm in 12 to 18 months.

Eligibility criteria: General Inclusion Criteria (GIC):

* GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable).
* GIC2: Age ≥ 18 years at the time of signing the informed consent
* GIC3: Gender: Male or female (premenopausal and postmenopausal)
* GIC4: ECOG performance status Grade 0-2
* GIC5: Estimated life expectancy \> 12 weeks at the start of investigational medicinal product (IMP) treatment.
* GIC6: Adequate organ function, evidenced by the following laboratory results within 30 days of the start of IMP:

  * Absolute neutrophil count ≥ 1,500/mm3
  * Platelet count ≥ 100,000/mm3
  * Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
  * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
  * Estimated Creatinine clearance (using Cockcroft-Gault formula) ≥ 60 mL/min for small molecules and \>30 mL/min for monoclonal antibodies unless otherwise specified in the Arm Specific Eligibility.

These cut-off values may be modified with supporting data for specific drug regimens.

* GIC7: Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of IMP treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. If male, they must agree to refrain from donating sperm during treatment.
* GIC8: Contraception: Women of childbearing potential and men must be willing to use adequate contraception for the duration of protocol treatment. Additional information regarding contraception for the specific treatment arm will be added to the drug arm description. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (e.g., non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).
* GIC9: Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy, to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
* GIC10: Participant compliance: Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Additional arm specific inclusion criteria as needed by drug arm regimen

General Exclusion Criteria (GEC):

* GEC1: Wash out periods: No other anticancer therapy within the following periods:

  * chemotherapy or investigational agents, 3 weeks
  * mitomycin C and nitrosoureas, 6 weeks
  * radiotherapy, 3 weeks
  * targeted therapy, 2 weeks
  * MAbs, ADCs, and immunotherapy, 3 weeks
  * endocrine therapy, no washout needed
* GEC2: Concurrent therapy with other Investigational Products.
* GEC3: Prior history of drug/regimen hypersensitivity: History of infusion-related reactions and/or hypersensitivity to IMP or excipients of the study drug/drugs which led to permanent discontinuation of the treatment.
* GEC4: Uncontrolled intercurrent illness including (active infection, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements).
* GEC5: Cardiovascular disease: History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, or baseline corrected QT by Fridericia's formula (QTcF) length \> 470 msec for men and women. The QTcF cut-off value may be modified with supporting data for specific drug regimens.
* GEC6: CNS tumoral spread: Active uncontrolled/symptomatic central nervous system cancer/spinal cord compression. Previously treated and clinically stable lesions, as per Investigator's judgment, are permitted. Newly discovered asymptomatic lesions that are not life threatening and do not require urgent local treatment to ensure patient safety, after consultation with study regimen chaperones, may be permitted.
* GEC7: Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis.
* GEC8: Recent major surgery within 4 weeks prior to start IMP treatment
* GEC9: Pregnancy or breastfeeding
* GEC10: Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
* GEC11: Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.
* GEC12: Concomitant malignancies: A diagnosis of a malignancy in the 2 years prior to starting study treatment other than the disease under study. Exceptions include indolent or definitively treated malignancy not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial.
* Additional arm specific exclusion criteria as needed by drug arm regimen

Primary outcomes:
measure: Incidence of Adverse Events related to the treatment
timeFrame: Start of treatment to 30 days post treatment (estimated 12 -18 months)
measure: Incidence of Dose Limiting Toxicities (DLTs) at each dose level
timeFrame: DLT observation period: Start of treatment to 21 days (Cycle 1)
measure: Maximum Tolerated Dose (MTD)
timeFrame: Start of treatment to the date of last participant at end of DLT observation period at highest dose level (estimated 6 months)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Start of treatment to the date of last participant at highest dose level (estimated 6 months)
measure: Overall Response Rate (ORR)
timeFrame: Start of treatment to 12 months
measure: Duration of Response (DOR)
timeFrame: Start of treatment to 12 months
Secondary outcomes:
measure: Progression Free Survival (PFS) - descriptive
timeFrame: Start of treatment to 12 months
measure: Clinical Benefit Rate (CBR) at 6 months
timeFrame: Start of treatment to 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
state: Alabama
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medicine Comprehensive Cancer Center
state: Illinois
city: New Lenox
country: United States
facility: UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Orland Park
country: United States
facility: UChicago Medicine Orland Park
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Paula R Pohlmann, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References: