Albumin-Bound Paclitaxel and Gemcitabine in Patients With Untreated Stage IV or Recurrent Squamous Cell Lung Cancers

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02525653
• Collaborator: Celgene Corporation (Industry), Miami Cancer Institute (Other)
• Enrollment: 40
• Locations: 6
• Arm: 1
• Actual Duration (Months): 45
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to test the safety and effectiveness of albumin-bound paclitaxel plus gemcitabine in patients with advanced squamous cell lung cancers. The investigators would like to determine the percentage of patients with squamous cell lung cancers who experience shrinkage of their tumors following treatment with this regimen. This combination of drugs is not a standard therapy for patients with squamous cell lung cancers. However, each of these drugs, when given alone or with other chemotherapies, is FDA-approved for the treatment of this disease.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Untreated Stage IV or Recurrent Squamous Cell Lung Cancers	Drug: albumin-bound paclitaxel; Drug: gemcitabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients With Untreated Stage IV or Recurrent Squamous Cell Lung Cancers
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Albumin-Bound Paclitaxel and Gemcitabine During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.

Drug: albumin-bound paclitaxel; Drug: gemcitabine

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [1 year]

   defined as the percentage of patients with complete or partial responses based on RECIST 1.1, at any time prior to disease progression, out of all evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

1. Participants Evaluated for Toxicity [1 year]

   AE's will be collected, tabulated according to CTCAE version 4.0 and summarized using descriptive statistics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed squamous cell lung cancer

• Newly diagnosed untreated Stage IV and/or recurrent after adjuvant therapy with metastatic disease

• Patients previously treated with immune checkpoint inhibitor therapy are eligible

• Measurable disease as per RECIST 1.1

• Greater than 6 months since receiving neo-adjuvant or adjuvant chemotherapy.

• Age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Women of childbearing potential and sexually active men enrolled in the study must agree to practice effective contraception method during treatment and for three months after completing treatment

• Negative serum or urine β-hCG pregnancy test at screening for patients of childbearing potential

• < Grade 2 pre-existing peripheral neuropathy (per CTCAE)

• Marrow and organ function as follows:

• ANC ≥ 1500 cells/mm3

• Platelets > 100,000 cells/mm3

• Hemoglobin>9g/dL

• Creatinine clearance ≥ 40mL/min

• Bilirubin ≤ 1.5 mg/dL

• AST/ALT≤2.5 x upper limit of normal range (ULN),

• alkaline phosphatase ≤ 2.5 X upper limit of normal, unless bone metastasis in present in the absence of liver metastasis

Exclusion Criteria:

• Prior treatment with albumin-bound paclitaxel or gemcitabine

• Prior systemic anticancer therapy for advanced squamous cell lung cancer

• Untreated brain metastasis. Patients with treated brain metastases who are off steroids are eligible

• Peripheral neuropathy greater than grade 1

• Malignancies within the past 5 years other than non-melanoma skin cancer or insitu cervical cancer status post treatment

• Patients with other serious medical illnesses including, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

• Class III or IV congestive heart failure by New York Heart Association

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miami Cancer Institute Baptist Health South Florida	Miami	Florida	United States	33143
2	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
3	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States
6	Memorial Sloan Kettering Westchester	Sleepy Hollow	New York	United States	10591

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Celgene Corporation
• Miami Cancer Institute

Investigators

• Principal Investigator: Paul Paik, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 12, 2019

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT02525653
• Other Study ID Numbers: 15-054
• First Posted: Aug 17, 2015
• Last Update Posted: Jan 12, 2021
• Last Verified: Sep 1, 2019

• Keywords provided by Memorial Sloan Kettering Cancer Center: Albumin-Bound; Paclitaxel; Gemcitabine; 15-054
• Additional relevant MeSH terms: Lung Neoplasms; Recurrence; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Albumin-Bound Paclitaxel and Gemcitabine
Arm/Group Description	During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Albumin-Bound Paclitaxel and Gemcitabine
Arm/Group Description	During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.
Overall Participants	40
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	28 70%
Male	12 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 12.5%
Not Hispanic or Latino	33 82.5%
Unknown or Not Reported	2 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 12.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5%
White	31 77.5%
More than one race	0 0%
Unknown or Not Reported	2 5%
Region of Enrollment (Count of Participants)
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	defined as the percentage of patients with complete or partial responses based on RECIST 1.1, at any time prior to disease progression, out of all evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albumin-Bound Paclitaxel and Gemcitabine
Arm/Group Description	During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.
Measure Participants	40
Partial Response	18 45%
Complete Response	1 2.5%
Not Evaluated, withdrew from study	5 12.5%
Stable Disease	12 30%
No Response	4 10%

2. Secondary Outcome

Title	Participants Evaluated for Toxicity
Description	AE's will be collected, tabulated according to CTCAE version 4.0 and summarized using descriptive statistics.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albumin-Bound Paclitaxel and Gemcitabine
Arm/Group Description	During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.
Measure Participants	40
Evaluable for toxicity	37 92.5%
Not evaluable for toxicity	3 7.5%

Adverse Events

Time Frame	1 year
Arm/Group Title	Albumin-Bound Paclitaxel and Gemcitabine
Arm/Group Description	During each 21-day cycle, albumin-bound paclitaxel at 100mg/mg2 over 120 minutes and gemcitabine at 1000mg/m2 over 30 minutes will be given intravenously on days 1 and 8 of each 21 day cycle. Treatment will continue until disease progression or intolerable side effects. After the 4th cycle of treatment, patients will have the option of discontinuing gemcitabine and proceeding with weekly albumin-bound paclitaxel as maintenance therapy.
All Cause Mortality
	Albumin-Bound Paclitaxel and Gemcitabine
	Affected / at Risk (%)	# Events
Total	21/40 (52.5%)
Serious Adverse Events
	Albumin-Bound Paclitaxel and Gemcitabine
	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)
Blood and lymphatic system disorders
Anemia	2/40 (5%)
Febrile neutropenia	2/40 (5%)
Cardiac disorders
Ventricular arrhythmia	1/40 (2.5%)
Gastrointestinal disorders
Colitis	1/40 (2.5%)
Diarrhea	2/40 (5%)
General disorders
Death NOS	6/40 (15%)
Edema limbs	1/40 (2.5%)
Fever	3/40 (7.5%)
Sudden death NOS	1/40 (2.5%)
Infections and infestations
Infections and infestations - Other, specify	1/40 (2.5%)
Lung infection	5/40 (12.5%)
Mucosal Infection	1/40 (2.5%)
Skin infection	2/40 (5%)
Urinary tract infection	1/40 (2.5%)
Injury, poisoning and procedural complications
Fall	1/40 (2.5%)
Hip fracture	1/40 (2.5%)
Investigations
Creatinine increased	2/40 (5%)
Platelet count decreased	1/40 (2.5%)
White blood cell decreased	1/40 (2.5%)
Metabolism and nutrition disorders
Anorexia	1/40 (2.5%)
Dehydration	1/40 (2.5%)
Hyperkalemia	2/40 (5%)
Musculoskeletal and connective tissue disorders
Back Pain	1/40 (2.5%)
Bone Pain	1/40 (2.5%)
Nervous system disorders
Peripheral motor neuropathy	1/40 (2.5%)
Seizure	1/40 (2.5%)
Transient ischemic attacks	1/40 (2.5%)
Renal and urinary disorders
Acute Kidney Injury	2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	1/40 (2.5%)
Dyspnea	3/40 (7.5%)
Hypoxia	2/40 (5%)
Pleural effusion	1/40 (2.5%)
Respiratory failure	3/40 (7.5%)
Vascular disorders
Hypotension	4/40 (10%)
Superficial thrombophlebitis	1/40 (2.5%)
Thromboembolic event	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Albumin-Bound Paclitaxel and Gemcitabine
	Affected / at Risk (%)	# Events
Total	37/40 (92.5%)
Blood and lymphatic system disorders
Anemia	37/40 (92.5%)
Gastrointestinal disorders
Nausea	3/40 (7.5%)
General disorders
Fatigue	4/40 (10%)
Investigations
Activated partial thromboplastin time prolonged	5/40 (12.5%)
Alanine aminotransferase increased	28/40 (70%)
Alkaline phosphatase increased	11/40 (27.5%)
Aspartate aminotransferase increased	25/40 (62.5%)
Blood bilirubin increased	7/40 (17.5%)
Creatinine increased	7/40 (17.5%)
INR increased	13/40 (32.5%)
Lymphocyte count decreased	24/40 (60%)
Neutrophil count decreased	15/40 (37.5%)
Platelet count decreased	25/40 (62.5%)
White blood cell decreased	25/40 (62.5%)
Metabolism and nutrition disorders
Hypercalcemia	4/40 (10%)
Hyperglycemia	37/40 (92.5%)
Hyperkalemia	12/40 (30%)
Hypoalbuminemia	35/40 (87.5%)
Hypocalcemia	19/40 (47.5%)
Hypoglycemia	4/40 (10%)
Hypokalemia	6/40 (15%)
Hypomagnesemia	9/40 (22.5%)
Hyponatremia	16/40 (40%)
Hypophosphatemia	2/40 (5%)
Musculoskeletal and connective tissue disorders
Hypernatremia	6/40 (15%)
Respiratory, thoracic and mediastinal disorders
Cough	4/40 (10%)
Dyspnea	3/40 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.