Modular Phase 1B Hypothesis-Testing, Biomarker-Driven, Talazoparib Combination Trial (TalaCom)
概览
- 阶段
- 1 期
- 干预措施
- Axitinib
- 疾病 / 适应症
- Advanced Malignant Solid Neoplasm
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 111
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicities
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES: I. To determine the safety and tolerability, and establish the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of the combination of talazoparib tosylate (talazoparib) with palbociclib isethionate (palbociclib) (Arm A), axitinib (Arm B), and crizotinib (Arm C) in patients with advanced solid tumors. II. To assess the safety and toxicity profile of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetic and pharmacodynamic profile of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). II. To obtain a preliminary assessment of the antitumor activity of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). III. To assess predictive biomarkers of response and resistance to the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). OUTLINE: This is a phase I, dose-escalation study. Patients are assigned to 1 of 3 arms. ARM A: Patients receive talazoparib orally (PO) once daily (QD) on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion. ARM B: Patients receive talazoparib PO QD on days 1-28 and axitinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion. ARM C: Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion. After the completion of study treatment, patients are followed up for 90 days and then every 12 weeks until progression of disease, receipt of another cancer drug, or for another two years.
研究者
入排标准
入选标准
- •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 specified below for each cohort 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. See below for additional eligibility guidance for Arms A - C:
- •Eligibility for Arm A (Talazoparib + Palbociclib):
- •Solid tumors with defects in DDR genes such as: BRCA1/2, PALB2, RAD51C/D, or other related genes at the discretion of the principal investigator, or
- •MYC-aberrant solid tumors (e.g. overexpression, amplification, mutation)
- •Eligibility for Arm B (Talazoparib + Axitinib):
- •Solid tumors with defects in DDR genes such as: BRCA1/2, PALB2, RAD51C/D, or other related genes at the discretion of the principal investigator, or
- •Participants with BRCA1/2 wild-type high-grade serous ovarian cancer, or
- •Participants with metastatic castration-resistant prostate cancer without a specific and/or selected mutation
- •Eligibility for Arm C (Talazoparib + Crizotinib):
排除标准
- •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.
- •Participants 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. Participants 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, participants who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout.
- •Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade \> 1). However, alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 adverse events not constituting a safety risk, based on the investigators 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.
- •Participants with known uncontrolled HIV virus or Acquired immunodeficiency syndrome. Note: Patients with history of controlled HIV virus will be considered eligible for this trial.
- •Participants with uncontrolled Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Note: Participants with controlled hepatitis B or hepatitis C will be considered eligible for this trial.
- •Clinically significant cardiovascular disease, including any of the following:
研究组 & 干预措施
Arm II (talazoparib, axitinib)
Patients receive talazoparib PO QD on days 1-28 and axitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Axitinib
Arm I (talazoparib, palbociclib)
Patients receive talazoparib PO QD on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Palbociclib Isethionate
Arm I (talazoparib, palbociclib)
Patients receive talazoparib PO QD on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Talazoparib Tosylate
Arm II (talazoparib, axitinib)
Patients receive talazoparib PO QD on days 1-28 and axitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Talazoparib Tosylate
Arm III (talazoparib, crizotinib)
Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Crizotinib
Arm III (talazoparib, crizotinib)
Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.
干预措施: Talazoparib Tosylate
结局指标
主要结局
Incidence of dose limiting toxicities
时间窗: Up to 30 days after the last investigational product administration
Incidence of dose limiting toxicities of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C) will be assessed. Severity of AEs will be graded according to the NCI CTCAE version 5.0.
Incidence of adverse events
时间窗: Up to 30 days after the last investigational product administration
Incidence and severity of adverse events and serious adverse events in patients being treated with the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). Severity of adverse events (AEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Tabulations will be produced for safety parameters.
次要结局
- Objective response(Up to 2 years)
- Progression free survival(Up to 2 years)
- Overall survival(Up to 2 years)
- Plasma pharmacokinetic (PK) parameters (maximum plasma concentration)(Up to 2 years)
- Plasma pharmacokinetic parameters (Ctrough)(Up to 2 years)
- Clinical benefit rate(Up to 2 years)
- Duration of response(Up to 2 years)
- Plasma pharmacokinetic (PK) parameters (time to maximum plasma concentration)(Up to 2 years)
- Plasma pharmacokinetic (PK) parameters (area under the plasma concentration)(Up to 2 years)
- Plasma pharmacokinetic parameters (maximum)(Up to 2 years)