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Report for Clinical Trial NCT01723800

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Phase I Trial of BKM120 in Combination With Carboplatin and Pemetrexed in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

This phase I trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with carboplatin and pemetrexed disodium in treating patients with stage IV non-small cell lung cancer. PI3K inhibitor BKM120 and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PI3K inhibitor BKM120, carboplatin, and pemetrexed disodium together may kill more tumor cells

NCT01723800 Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

6 Interventions

Name: PI3K inhibitor BKM120

Description: Given PO
Type: Drug
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Name: pemetrexed disodium

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Name: carboplatin

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Name: laboratory biomarker analysis

Description: Correlative studies
Type: Other
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Name: pharmacological study

Description: Correlative studies
Type: Other
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Name: quality-of-life assessment

Description: Ancillary studies
Type: Procedure
Group Labels: 1

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)


Primary Outcomes

Measure: Maximum tolerated dose, defined as the highest dose in which fewer than 33% of study participants experience a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) CTCAE version 4.0

Time: 21 days

Description: Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.

Measure: Toxicity profile of PI3K inhibitor BKM120, assessed using NCI CTCAE version 4.0

Time: Up to 28 days after completion of study treatment

Secondary Outcomes

Description: Means and 95% confidence intervals will be provided for the PK parameters.

Measure: Pharmacokinetic (PK) parameters of PI3K inhibitor BKM120, carboplatin, and pemetrexed disodium in combination

Time: Days 1 and 8 of course 1

Description: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

Measure: Anti-tumor activity (complete response [CR] + partial response [PR]), assessed using RECIST

Time: Up to 28 days after completion of study treatment

Description: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

Measure: Disease control rate (CR + PR + stable disease [SD]), assessed using RECIST

Time: Up to 28 days after completion of study treatment

Description: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

Measure: Progression free survival

Time: 6 months

Description: Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

Measure: Overall survival

Time: 1 year

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 P13K

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.. Inclusion Criteria: - Patients who have signed a written informed consent - Patients must have a histologic or cytologic diagnosis of advanced, nonsquamous NSCLC (stage IV by American Joint Committee on Cancer [AJCC] 7th edition [ed.]) - Patients should not have received prior systemic chemotherapy for metastatic disease (prior epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], kinase inhibitor therapy is allowed); prior adjuvant or neoadjuvant therapy for early stage disease is allowed if received >= 12 months prior to study entry - Prior radiation therapy is allowed to < 25% of the bone marrow; prior radiation must be completed at least 2 weeks prior to day 1 of cycle 1, and patients must have recovered from the acute toxic effects - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal (LLN) - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3 x upper limit of normal [ULN] if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present) - Serum creatinine =< 1.5 x ULN or calculated or 24-hour clearance >= 45 mL/min (calculated creatinine clearance based on Cockcroft-Gault formula) - Serum phosphorus >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) =< 2 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor or mammalian target of rapamycin (mTOR)-directed inhibitor - Patients with a known hypersensitivity of BKM120 or to its excipients - Patients with anaplastic lymphoma kinase (ALK) rearrangement or an activating epidermal growth factor receptor (EGFR) mutation who have not received and progressed on appropriate tyrosine kinase inhibitor therapy - Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 2 weeks from therapy completion (incl. --- P13K ---

age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 months in total after study drug discontinuation); the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male should be the sole partner for that patient - Use of a combination of any two of the following (a + b): - a) Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, defined as all males physiologically capable of conceiving offspring, must use a condom during treatment, for 5 T1/2 (8 days) after stopping treatment and for an additional 12 weeks (3 months in total after study drug discontinuation) and should not father a child in this period - Known diagnosis of human immunodeficiency virus (HIV) infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator - Patient has acute viral hepatitis or a history of chronic or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, (typically defined by elevated AST/ALT [persistent or intermittent], high HBV deoxyribonucleic acid [DNA] level hepatitis B virus surface protein antigen [HBsAg] positive, or high HCV ribonucleic acid [RNA] level) (testing not mandatory) Inclusion Criteria: - Patients who have signed a written informed consent - Patients must have a histologic or cytologic diagnosis of advanced, nonsquamous NSCLC (stage IV by American Joint Committee on Cancer [AJCC] 7th edition [ed.]) - Patients should not have received prior systemic chemotherapy for metastatic disease (prior epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], kinase inhibitor therapy is allowed); prior adjuvant or neoadjuvant therapy for early stage disease is allowed if received >= 12 months prior to study entry - Prior radiation therapy is allowed to < 25% of the bone marrow; prior radiation must be completed at least 2 weeks prior to day 1 of cycle 1, and patients must have recovered from the acute toxic effects - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal (LLN) - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3 x upper limit of normal [ULN] if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present) - Serum creatinine =< 1.5 x ULN or calculated or 24-hour clearance >= 45 mL/min (calculated creatinine clearance based on Cockcroft-Gault formula) - Serum phosphorus >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) =< 2 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor or mammalian target of rapamycin (mTOR)-directed inhibitor - Patients with a known hypersensitivity of BKM120 or to its excipients - Patients with anaplastic lymphoma kinase (ALK) rearrangement or an activating epidermal growth factor receptor (EGFR) mutation who have not received and progressed on appropriate tyrosine kinase inhibitor therapy - Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 2 weeks from therapy completion (incl. --- P13K ---



HPO Nodes


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