Clinical trial NCT03913455: Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer
Official title: A Phase II Study Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Extensive-stage Small Cell Lung Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Astex Pharmaceuticals, Inc.
name: Indiana University School of Medicine
First posted: 2019-04-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II, open-label, single arm, single-stage study. Both, chemo-sensitive and chemo-resistant patients will be enrolled and treated with 4 cycles of combination of Guadecitabine and carboplatin


Eligibility criteria: Inclusion Criteria:

* Male or female subjects, age ≥ 18 years.
* Histological or cytological diagnosis of small cell lung cancer. Subjects must have extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases.
* Patient should not have received more than 1 prior line of chemotherapy (could have received immunotherapy which does not count as chemotherapy).
* ECOG PS 0-1
* Measurable disease as per RECIST v1.1. Subjects may have bone-only disease. NOTE: Bone-only subjects are eligible if their disease can be documented/evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria. NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.
* Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements:

  * Hemoglobin ≥ 9.0 g/dL
  * Absolute neutrophil count (ANC) ≥ 1,500/mm3
  * Platelet count ≥ 100,000/mm3
  * Total bilirubin ≤ 1.5 x upper limit of normal (ULN). For subjects with Gilbert's Disease, total bilirubin ≤ 3 x ULN
  * ALT and AST ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5×ULN
  * International Normalized Ratio (INR) ≤1.5, if not therapeutically anticoagulated. Subjects who are being therapeutically anticoagulated may be included provided that the anticoagulation regimen is stable and closely monitored.
  * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2 as determined using the Cockcroft-Gault formula.
* Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
* Male and female subjects of child- bearing potential must agree to use an effective method of birth control from the screening visit through 6 months after the last dose of study drug.

Exclusion Criteria:

* Platinum refractory disease defined as disease progression during first line platinum containing chemotherapy regimen. Progression following platinum based therapy is allowed.
* Prior therapy with a hypomethylating agent.
* Previously untreated (non-irradiated), symptomatic brain metastases. No prior treatment is required for non-symptomatic brain metastases. Previously treated symptomatic brain metastases are permitted.
* Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
* Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.)
* Hypersensitivity to (IMP) or components of the study treatment regimen.
* Treated with any investigational drug within 3 weeks of first dose of study treatment.
* Pregnant or breastfeeding.
* Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 7 months.
Secondary outcomes:
measure: Adverse Events
timeFrame: AEs had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 5 months
measure: Objective Response Rate (ORR)
timeFrame: Up to a maximum of 7 months
measure: Disease Control Rate (DCR)
timeFrame: Up to a maximum of 7 months
measure: Overall Survival (OS)
timeFrame: Time of treatment start until death or date of last contact, up to a maximum of 16 months.
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Univeristy Melvin and Bren Simon Cancer Center
state: Indiana
city: Muncie
country: United States
facility: IU Health Ball Memorial Cancer Center
state: Indiana
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Milwaukee
country: United States
facility: University of Wisconsin, Clinical Cancer Center
state: Wisconsin
Study officials:
affiliation: Indiana University School of Medicine
name: Shadia Jalal, MD, MBBS
role: PRINCIPAL_INVESTIGATOR
References: