Moffitt logo

Clinical Trials Search

Clinical Trial 18810

Cancer Type: Breast
Interventions:772256 (Palbociclib); Faslodex (fulvestrant); Femara (Letrozole); Gedatolisib; Letrozole; PF-05212384 (Gedatolisib); Palbociclib; fulvestrant

Study Type: Treatment
Phase of Study: Phase I

  • Heather Han

Call 813-745-6100
or 1-800-679-0775

Study Title

Phase 1b Study To Assess The Safety, Tolerability, and Clinical Activity of Gedatolisib in Combination with Palbociclib and Either Letrozole Or Fulvestrant in Women with Metastatic or Locally Advanced/Recurrent Breast Cancer (Mbc)


The purpose of this research study is to learn about the effects of the study drug, gedatolisib, when given in combination with the typical dose of other drugs to treat breast cancer and to find the best dose of gedatolisib in combination with these drugs. The study is made up of two parts. In the first part (called the dose escalation phase), participants will be treated with different dose levels of gedatolisib in combination with palbociclib/letrozole or palbociclib/fulvestrant. This is done in order to determine the maximum tolerated dose or MTD of gedatolisib that will be used in the second part of the study. In the second part (called the dose expansion phase), there will be three groups (arms) of participants: Arm A: Gedatolisib in combination with palbociclib/letrozole (for participants who have not received any endocrine-based therapy). Arm B: Gedatolisib in combination with palbociclib/fulvestrant (for participants who have not been previously treated with palbociclib). Arm C: Gedatolisib in combination with palbociclib/fulvestrant (for participants who have been previously treated with palbociclib). Which group participants are assigned to will depend on their cancer history and what treatments they have already received.


Primary Objective Dose Escalation: To assess the safety, tolerability, and MTD of the triplet combination of gedatolisib added to either the standard dose of the palbociclib/letrozole or palbociclib/fulvestrant. Dose Expansion: To determine if the triplet combination of gedatolisib plus palbociclib/letrozole or gedatolisib plus palbociclib/fulvestrant produces a superior objective response (OR) in patients with mBC, compared to historical control data of the doublet combination of palbociclib plus either letrozole or fulvestrant. Secondary Objectives: To further assess the safety and tolerability of the combinations tested in the study. To assess anti-tumor activity in the dose escalation portion. To assess additional efficacy parameters in the expansion portion, including duration of response (DR) and progression free survival (PFS). To characterize the potential for prolonged QTc interval. To assess the single dose and multiple dose pharmacokinetics (PK) of gedatolisib and palbociclib, and the multiple dose pharmacokinetics of fulvestrant and letrozole.

Inclusion Criteria

  • Women 18 years of age or older, who are either: Postmenopausal or Pre/perimenopausal women with medically-induced menopause by treatment with agents to induce chemical menopause.
  • Histologically or cytologically proven diagnosis of breast cancer with evidence of metastasis.
  • Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
  • Dose Escalation Portion: Participants must satisfy one of the following criteria:
  • Letrozole combination cohort (L): metastatic breast cancer (MBC) with progression who are candidates for a letrozole-containing regimen, with palbociclib.
  • Fulvestrant combination cohort (F): MBC with progression who are candidates for a fulvestrant containing regimen, with palbociclib.
  • Dose Expansion Portion: Participants must satisfy one of the following criteria:
  • Arm A: MBC with progression and no prior endocrine based systemic therapy in the metastatic setting;
  • Arm B: MBC with progression during or following one prior endocrine based systemic therapy in the metastatic setting, with no prior therapy with any cyclin-dependent kinase (CDK) inhibitor;
  • Arm C: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor.
  • Arm D: MBC having progressed on a CDK inhibitor in combination with endocrine therapy as the most recent regimen for metastatic disease (only one or two prior lines of endocrine therapy are allowed), in which gedatolisib is administered on a three weeks on/one week off schedule.
  • Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  • Bone only patients during dose escalation portion.
  • Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
  • Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.
  • Adequate bone marrow, renal and liver function.

  • Exclusion Criteria

  • Prior treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.
  • More than 1 line of prior chemotherapy in the treatment of metastatic or locally advanced/recurrent disease.
  • Bone only patients during expansion/efficacy portion.
  • Potential participants with advanced/metastatic disease who have symptomatic visceral spread, and who have life threatening complications needing immediate therapy, such as massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver replacement with tumor.
  • Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases.
  • Active bacterial, fungal or viral infection.
  • Uncontrolled or significant cardiovascular disease.
  • External beam radiation therapy consisting of 4-6 weeks of fractionated treatment within 4 weeks of investigational product.
  • Cytotoxic chemotherapy within 4 weeks of investigational product (6 weeks for mitomycin C or nitrosoureas) if immediate prior regimen was administered on an every 3 4 week schedule or 2 weeks of investigational product if immediate prior regimen consisted of weekly therapy.
  • Any other anti-cancer agents (e.g., hormonal, biological, investigational) within 5 times the half-life prior to investigational product.
  • Impairment of gastrointestinal (GI) function or GI disease.
  • Females who are pregnant or breastfeeding; and females of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for 90 days.
  • Other exclusions may apply