Phase I Study of Combination of Gedatolisib With Palbociclib and Faslodex in Patients With ER+/HER2- Breast Cancer

NCT02626507 | Unknown Phase 1

• 1 other identifier: CL- Gedatolisib-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a dose-escalation Phase Ib clinical trial in 18 patients with newly diagnosed Stage I-IV ER+/HER2- breast cancer, with the primary cancer in place. These patients have not received prior therapy for their breast cancer and intend to undergo surgery after four cycles of therapy. This is an open-label study, and investigators and subjects are not blinded to the treatment. The reason for using an open-label study design is because this is a dose-escalation trial, and the investigators need to determine the potential toxicity before a decision can be made to continue the dose escalation procedures. The assignment of patients will not be randomized, as this is a dose-escalation trial.

Conditions

Breast Cancer

Keywords

ER+/HER2

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  safety, tolerability,potential efficacy and MTD of Gedatolisib and MTD used in combination with palbociclib and Faslodex, in patients with

  12-24 months

Secondary Outcomes (1)

• Number of participants with treatment-related pathological Complete Response (pCR)

  1 year

Study Arms (1)

Gedatolisib ER+/HER2- Breast Cancer

EXPERIMENTAL

* Gedatolisib at escalating doses of 180, 215 and 260 mg via a 3-6 dose-escalation scheme is administered once weekly on the first day for each of the four weeks during the four 4-week cycles. * Faslodex at 500 mg is administered IM into the buttocks slowly (over 1 - 2 minutes per injection) as two 5-mL injections, one in each buttock, on Days 1 and 15 of Cycle 1 and on Day 1 of the remaining three 4-week treatment cycles. * Palbociclib at 125 mg is administered PO with food daily on Days 1-21 for each of the four 4-week cycles * Zoladex is used to render menopause in pre-menopausal subjects, given once every 28 days starting at least 14 days prior to treatment.

Drug: Gedatolisib; Drug: Faslodex; Drug: Palbociclib; Drug: Zoladex

Interventions

Gedatolisib DRUG

adenosine triphosphate (ATP) competitive, highly selective and potent inhibitor of pan-class I isoform phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3-K)

Also known as: Code name PF-05212384, PKI-587

Gedatolisib ER+/HER2- Breast Cancer

Faslodex DRUG

Faslodex® (Fulvestrant) is a potent anti-estrogen drug that binds and degrades estrogen receptors (ERs).

Also known as: Fulvestrant

Gedatolisib ER+/HER2- Breast Cancer

Palbociclib DRUG

Palbociclib (Ibrance®) is an orally active highly selective reversible inhibitor of cyclin-dependent kinase (CDK) 4 and CDK 6.

Also known as: Ibrance

Gedatolisib ER+/HER2- Breast Cancer

Zoladex DRUG

Zoladex is used to render menopause in pre-menopausal subjects, given once every 28 days starting at least 14 days prior to treatment.

Also known as: goserelin

Gedatolisib ER+/HER2- Breast Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Stage I-IV, with primary cancer in place, non-inflammatory invasive breast cancer confirmed by core needle or incisional biopsy (excisional biopsy is not allowed):
• the disease is ER+ (defined as ER expression \>10% of invasive cancer cells according to immunohistochemical \[IHC\] staining)
• HER2- (defined as IHC staining of 0 to 1+ or fluorescence in situ hybridization \[FISH\] ratio of HER2 gene copy/chromosome 17 of \<2.0.)
• the disease is previously untreated for breast cancer, operable and intend to undergo surgery for her disease (e.g., a mastectomy or lumpectomy) after completion of neoadjuvant therapy
• the disease must be measurable, defined as clinically or radiographically measureable target lesion in the breast that is ≥1 cm in diameter
• the disease cannot be axillary disease only (i.e., no identifiable tumor in the breast that is ≥1 cm on physical exam or radiographic study)
• the disease can be multi-centric or bilateral disease, provided the target lesion meets the above eligibility criteria
• breast cancer patients with lobular and luminal histology will be included. However, patients with lobular histology should not be more than a quarter of the total number of patients in this trial, as the investigational drugs are likely to have greater activities in patients with luminal histology.
• (Note 1: In patients with Stage III disease, imaging studies is performed to rule out overt metastatic disease. In patients with clinically positive axillae, histologic confirmation by biopsy or fine-needle aspiration is performed. Patients with clinically negative axillae can undergo pretreatment sentinel lymph node sampling.) (Note 2: In patients with Stage IV disease, the disease must be of low burden. Low burden is defined in this study as no more than one metastatic site in the liver or lung, or up to three metastatic sites in the bone, regardless of the number of lymph nodes per latest radiographic scan. If a patient is found to have metastatic disease on scan(s) performed after patient completes study neoadjuvant therapy, surgery will not be performed and patients will be excluded from this study.)
• B. Females ≥18 years of age.
• C. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use effective contraceptive methods (such as abstinence, intrauterine device \[IUD\], or double barrier device) during the study, and must have a negative serum or urine pregnancy test within one week prior to treatment initiation.
• D.Mentally competent, able to understand and willingness to sign the informed consent form.
• E.At least 4 weeks must have elapsed from any prior major surgery or hormonal therapy. The following procedures are not considered major surgical procedure:
• Obtaining the required research needle biopsies
• Placement of a radiopaque clip to localize a tumor or tumors for subsequent surgical resection

You may not qualify if:

• A.Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 6 months, uncontrolled or symptomatic cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.
• B. A marked baseline prolongation of QT/QTc interval (e.g., repeated exhibition of a QTc interval \>470 ms).
• C. A history of additional risk factors for torsade de pointes (e.g., clinically significant heart failure, hypokalemia, family history of Long QT Syndrome).
• D. Arterial thrombotic event, stroke, or transient ischemia attack within the past 12 months.
• E. Uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>90 mm Hg), or peripheral vascular disease ≥grade 2.
• F.Active central nervous system (CNS), epidural tumor or metastasis, or brain metastasis.
• G.Any active uncontrolled bleeding, a bleeding diathesis (e.g., active peptic ulcer disease), or a history of bleeding (e.g., hemoptysis, upper or lower gastrointestinal bleeding) within the past 6 months.
• H.Dyspnea with minimal to moderate exertion. Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly). Patients with any amount of clinically significant pericardial effusion.
• I.Diabetes of any type, except non-insulin dependent diabetes mellitus .(NIDDM) that is controlled and with hemoglobin A1c \<8%.
• J.Evidence of active infection during screening, or serious infection within the past month.
• K.Patients with known HIV infection.
• L.Serious or non-healing wound, skin ulcer, or bone fracture.
• M.Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
• N.Neuropathy of grade ≥2.
• O.Albumin \<2.5 g/dL or \<25 g/L.

Sponsors & Collaborators

• Hoffman Oncology: lead
• DSCS CRO: collaborator

Study Sites (2)

California Research Institute

Los Angeles, California, 90027, United States

Location

Hoffman Oncology

The Bronx, New York, 10469, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

gedatolisib; Fulvestrant; palbociclib; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Anthony Hoffman, MD

  Hoffman Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 10, 2015
• Study Start: January 1, 2016
• Primary Completion: February 15, 2022
• Study Completion: March 15, 2022
• Last Updated: February 9, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)