Overview

Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial

Status:
Recruiting
Trial end date:
2025-09-03
Target enrollment:
0
Participant gender:
All
Summary
This phase Ib trial is to find out the best dose, possible benefits and/or side effects of talazoparib when given in combination with palbociclib, axitinib, or crizotinib in treating patients with solid tumors that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). PARPs are proteins that help repair damaged DNA, the genetic material that serves as the body's instruction book. PARP inhibitors, such as talazoparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Palbociclib, axitinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib in combination with palbociclib, axitinib, or crizotinib may help control locally advanced or metastatic solid tumors.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Axitinib
Crizotinib
Palbociclib
Talazoparib
Criteria
Inclusion Criteria:

- Pathogenic or likely pathogenic germline or somatic gene defect as determined by local
assessment and classification in at least one of the following:

- Defect in DNA damage response (DDR) genes such as: BRCA1/2, PALB2, RAD51C/D, or
other related genes at the discretion of the principal investigator in
consultation with the MD Anderson Cancer Center Institute for Personalized Cancer
Therapy Precision Oncology Decision Support (PODS) group (Arms A-C)

- Defect in MET, ALK or ROS1, e.g. MET mutations or amplifications, high MET
expression, ALK translocations, ROS1 translocations (eligible for Arm C:
talazoparib + crizotinib)

- NOTE: Patients with metastatic castration-resistant prostate cancer can enroll in
Arm B with talazoparib + axitinib without a specific and/or selected mutation

- Patients who are eligible for more than one Arm will be assigned according to
physician preference

- Histological or cytological diagnosis of a solid tumor that is advanced/metastatic,
intolerable to standard therapy, resistant to effective standard therapy, or for which
no standard therapy is available

- Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery
or a metastatic tumor biopsy; the sample must have been obtained within 12 months
prior to study enrollment. When only bone disease is present, an archival tumor tissue
sample obtained within 5 years prior to study enrollment may be accepted for
non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate
cancer patients only NOTE: A fresh biopsy should be encouraged for all patients at
time of enrollment even if a previous biopsy is available. Optional on-treatment and
at-progression biopsies will be encouraged for all patients

- Have measurable disease at study enrollment as defined by RECIST v1.1 with at least 1
measurable lesion that has not previously been irradiated; or patients may have bone
metastatic disease evaluable by Prostate Cancer Working Group 2 (PCWG2) for subjects
with metastatic castration-resistant prostate cancer (mCRPC), or according to the
tumor evaluation criteria best suited and accepted for the tumor type being evaluated)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1

- Absolute Neutrophil Count (ANC) >= 1,500/mm^3 or >= 1.5 x 10^9/L (without
hematopoietic growth factor or transfusion support within 14 days prior to study
enrollment)

- Platelets >= 100,000/mm^3 or >= 100 x 10^9/L (without hematopoietic growth factor or
transfusion support within 14 days prior to study enrollment)

- Hemoglobin >= 9 g/dL (>= 5.6 mmol/L) (without hematopoietic growth factor or
transfusion support within 14 days prior to study enrollment)

- estimated creatinine clearance >= 60 mL/min will be required during dose-escalation
phase, according to the Cockcroft-Gault formula

- Where creatinine clearance (CLCR) (creatinine clearance) is measured in mL/min,
age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine)
in mg/dL

- Or as measured by 24h urine assessment NOTE: Patients with moderate renal
impairment (30-59 mL/min) will be considered during the dose expansion phase. A
reduced starting dose for talazoparib will be considered in these patients

- Total serum bilirubin =< 1.5 x the upper limit of normal range (ULN)

- Aspartate and Alanine aminotransferase (aspartate aminotransferase [AST] and alanine
aminotransferase [ALT]) =< 5 x ULN

- Female Patients of childbearing potential must have negative serum pregnancy or urine
pregnancy test at screening. Female patients of non-childbearing potential must meet
at least one of the following criteria:

- Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause and have a serum follicle-stimulating hormone (FSH) level
confirming the postmenopausal state

- Have undergone a documented hysterectomy and/or bilateral oophorectomy

- Have medically confirmed ovarian failure All other female patients are considered
to be of childbearing potential

- Evidence of a personally signed and dated informed consent document, within > 28 days
prior to enrollment, indicating that the patient has been informed of all pertinent
aspects of the study

- Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures

- Able to swallow the study drug, have no known intolerance to study drugs or
excipients, and comply with study requirements

Exclusion Criteria:

- Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation
therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to
metastatic lesion(s) is permitted, provided it has been completed at least 2 days
prior to study enrollment and no clinically significant toxicities are expected (e.g.
mucositis, esophagitis)

- Major surgery within 4 weeks prior to study enrollment

- Patients with known hypersensitivity to either talazoparib or the additional study
drug to be received per treatment arm: palbociclib (Arm A), axitinib (Arm B),
crizotinib (Arm C)

- Diagnosis of myelodysplastic syndrome (MDS)

- Known symptomatic brain metastases requiring steroids. Patients with previously
diagnosed brain metastases are eligible if they have completed their treatment and
have recovered from the acute effects of radiation therapy or surgery prior to study
enrollment, have discontinued corticosteroid treatment for these metastases for at
least 2 weeks, and are neurologically stable. Of note, patients who required a single
dose of corticosteroids on days receiving radiation treatment do not require a 2-week
washout

- Participation in other studies involving investigational drug(s) within 4 weeks prior
to study entry and/or during study participation

- Persisting toxicity related to prior therapy (National Cancer Institute [NCI] Common
Terminology Criteria for Adverse Events [CTCAE] version [v]5.0 Grade > 1). However,
alopecia and sensory neuropathy Grade =< 2, or other Grade =< 2 adverse events not
constituting a safety risk, based on the investigator's judgement, are acceptable

- Active infection requiring systemic therapy. Minor infections, e.g. periodontal
infection or urinary tract infection (UTI), which may be treated with short term oral
antibiotics are allowed

- Patients with known uncontrolled human immunodeficiency virus (HIV) virus or acquired
immunodeficiency syndrome. Note: Patients with history of controlled HIV virus will be
considered eligible for this trial

- Patients with uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection at screening. Note: Patients with controlled hepatitis B or hepatitis C will
be considered eligible for this trial

- Clinically significant cardiovascular disease, including any of the following:

- Myocardial infarction or symptomatic cardiac ischemia within 6 months before
screening

- Congestive heart failure New York Heart Association class III or IV

- History of clinically significant ventricular arrhythmias (eg, sustained
ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1
year before screening

- History of Mobitz II second degree or third degree heart block unless a permanent
pacemaker is in place

- Hypotension as indicated by systolic blood pressure < 86 mm Hg at screening

- Bradycardia as indicated by a heart rate of <45 beats per minute on the screening
electrocardiogram

- Uncontrolled hypertension as indicated by systolic blood pressure > 170 mm Hg or
diastolic blood pressure > 105 mm Hg at screening

- Current use of potent P-gp inhibitors within 7 days prior to enrollment: amiodarone,
carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin,
glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir,
propafenone, quinidine, ranolazine, ritonavir, saquinavir,
sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tipranavir, valspodar, and verapamil.

- NOTE: Patients who have recently been on enzalutamide require a 28 day washout
period due to longer elimination half-life of this therapy

- Patients treated within the last 7 days prior to enrollment with:

- Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors
(ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine,
diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole,
lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole,
ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and
grapefruit or grapefruit juice). Drugs that are known to be strong CYP3A4
inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin,
primidone, rifabutin, rifampin, rifapentin, and St. John's wort

- Inability to swallow capsules, known malabsorption syndrome, or other conditions that
may impair absorption of study drugs

- Bisphosphonate or denosumab dosage that was not stable (i.e. not the same) for at
least 2 weeks before study enrollment for patients receiving these therapies

- Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgement of the investigator, would make the patient inappropriate for entry into
this study

- Medical, psychological, or social conditions that may interfere with the patient's
participation in the study, or with the evaluation of the study results

- Diagnosis of any other malignancy within 2 years prior to study enrollment, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of
the breast, bladder, or cervix, or low grade (Gleason =< 6) prostate cancer on
surveillance without any plans for treatment intervention (e.g. surgery, radiation, or
castration), or other early-stage low risk cancers

- Pregnant female patients; breastfeeding female patients; fertile male patients; and
female patients of childbearing potential who are unwilling or unable to use 2 methods
of contraception for the duration of the study and for at least 7 months after the
last dose of study drugs for female patients or 4 months after the last dose of study
drugs for male patients, whichever is later for the individual patient. Male patients
are prohibited from sperm donation while enrolled in this study and for 4 months after
the last dose of the study drugs. Highly effective methods of contraception are those
that alone or in combination, result in a failure rate of less than 1% per year when
used consistently and correctly. These methods include:

- Established use of oral, inserted, or injected or implanted hormonal methods of
contraception are allowed provided the patient remains on the same treatment
throughout the entire study and has been using that hormonal contraceptive for an
adequate period of time to ensure effectiveness

- Correctly placed copper containing intrauterine device (IUD)

- Male condom or female condom used with spermicide (i.e. foam, gel, film, cream or
suppository)

- Male sterilization with appropriately confirmed absence of sperm in the
postvasectomy ejaculate

- Bilateral tubal ligation or bilateral oophorectomy