A Study of LY2940680 in Small Cell Lung Cancer

Lilly

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Small Cell Lung Carcinoma

Treatments: Drug: Carboplatin; Drug: Placebo; Drug: LY2940680; Drug: Etoposide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01722292

2012-003174-83 (EudraCT Number)

14631

I4J-MC-HHBE (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to find a recommended dose of LY2940680 that can be safely given in combination with etoposide and carboplatin followed by LY2940680 alone in participants with extensive-disease small cell lung cancer. The study will also compare progression-free survival in participants who are administered etoposide, carboplatin and LY2940680 followed by LY2940680 alone versus etoposide, carboplatin, and placebo followed by placebo alone.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological or cytological diagnosis of Small Cell Lung Cancer (SCLC), including malignant pleural effusion that is extensive stage per the International Staging System

• Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance status schedule

• No prior systemic chemotherapy, immunotherapy, or biological therapy for SCLC

• Prior radiation therapy allowed to <25% of the bone marrow. Participants who have received prior radiation to the whole pelvis or chest for the treatment of SCLC are not eligible

• At least 1 unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• Adequate organ function including the following:

  • Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥1.5 x 10^9/ liter (L), platelets ≥100 x 10^9/L, and hemoglobin ≥9 grams/deciliter (g/dL)
  • Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3.0 x ULN (AP, AST, and ALT ≤5 x ULN is acceptable if liver has tumor involvement)
  • Renal: calculated creatinine clearance (CrCl) ≥50 milliliters per minute (mL/min) based on the standard Cockcroft and Gault formula

• Estimated life expectancy of at least 12 weeks

• For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment period; must have a negative serum pregnancy test within 7 days before study enrollment. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period

• Availability of a tumor tissue sample

• Able to swallow capsules

Exclusion criteria

• Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have previously participated in a study involving LY2940680
• Have previously received treatment with carboplatin or etoposide
• Have a mixed histological diagnosis of SCLC and Non-Small Cell Lung Cancer (NSCLC)
• Have a serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol
• Have an active infection [≥38.5 degrees Celsius and/or receiving Intravenous (IV) antibiotic therapy]
• Have a serious cardiac condition
• Have had a prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Participants with a history of non-metastatic prostate cancer, including biochemical relapse only, will be eligible even if diagnosed less than 5 years previously
• Symptomatic central nervous system (CNS) metastases and asymptomatic CNS metastases requiring concurrent corticosteroid therapy. Treated stable CNS metastases are allowed; the participant must be stable after radiotherapy for ≥2 weeks and off of corticosteroids for ≥1 week
• Presence of clinically significant third-space fluid collections that cannot be controlled prior to study entry
• Significant weight loss (that is, ≥10%) over the 6-week period prior to study entry
• Concurrent administration of any other antitumor therapy. An exception will be made for non-metastatic prostate cancer participants continuing androgen blockade therapy only or breast cancer participants continuing adjuvant antiestrogen therapy only (for example, an aromatase inhibitor)
• Females who are breastfeeding
• Have corrected QT interval (QTc) of >470 millisecond (msec) on screening electrocardiogram (ECG)
• Have received medications that are strong inhibitors of Cytochrome P450 3A4 (CYP3A4) within 7 days prior to receiving study drug

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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26 participants in 3 patient groups, including a placebo group

Phase 1b: LY2940680 + C + E

Experimental group

Description:

Phase 1b Dose Escalation: Cycles 1-6 (21 day cycles) LY2940680 administered orally, once daily at escalating doses (100 milligrams \[mg\] up to 400 mg) in combination with etoposide (E) 100 milligram per square meter (mg/m\^2) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle and carboplatin (C) Area Under the Curve \[AUC\] 5 (mg•min/mL) administered by IV infusion on day 1 each cycle. Phase 1b Maintenance: Cycles 7+ (21 day cycles) LY2940680 administered orally, once daily at the same dose as induction. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: LY2940680

Phase 2: Placebo + C + E

Placebo Comparator group

Description:

Induction: Cycles 1-6 (21 day cycles) Placebo administered orally once daily in combination with etoposide 100 mg/m2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle. Maintenance: Cycles 7+ (21 day cycles) Placebo administered orally once daily. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Placebo

Phase 2: LY2940680 + C+ E

Experimental group

Description:

Induction: Cycles 1-6 (21 day cycles) LY2940680 (dose to be determined in Phase 1b portion) administered orally once daily in combination with etoposide 100 mg/m\^2 administered by IV infusion on days 1, 2, 3 of each cycle and carboplatin AUC 5 administered by IV infusion on day 1 each cycle. Maintenance: Cycles 7+ (21 day cycles). LY2940680 (dose to be determined in Phase 1 portion) administered orally once daily.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: LY2940680