Phase II Study of Abraxane and Gemicitabine in Patients With Advanced Adenocarcinoma Non-Small Cell Lung Cancer Progressing After First-Line Platinum-Based Chemotherapy

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02303977
• Collaborator: (none)
• Enrollment: 37
• Arm: 1
• Actual Duration (Months): 58.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to see how well the combination of Abraxane and gemcitabine works in people with advanced adenocarcinoma NSCLC who have already had treatment for their disease. Gemcitabine and Abraxane are FDA approved chemotherapies; however, the FDA has not approved this combination in the treatment of this specific type of cancer. Patients may continue to receive the study drugs until their disease gets worse or they have unacceptable side effects.

Condition or Disease	Intervention/Treatment	Phase
Patients With Stage IV or Recurrent Adenocarcinoma of the Lung	Drug: Abraxane; Drug: Gemcitabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: a prospective, single-arm, non-randomized, phase II trial designed to evaluate the efficacy of combination gemcitabine and albumin-bound paclitaxel for advanced adenocarcinoma non-small cell lung cancer progressing after first-line platinum-based chemotherapy.a prospective, single-arm, non-randomized, phase II trial designed to evaluate the efficacy of combination gemcitabine and albumin-bound paclitaxel for advanced adenocarcinoma non-small cell lung cancer progressing after first-line platinum-based chemotherapy.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Abraxane and Gemicitabine in Patients With Advanced Adenocarcinoma Non-Small Cell Lung Cancer Progressing After First-Line Platinum-Based Chemotherapy
• Actual Study Start Date: Jun 26, 2015
• Actual Primary Completion Date: Apr 30, 2020
• Actual Study Completion Date: Apr 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine + Paciltaxel All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.	Drug: Abraxane; Drug: Gemcitabine

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Averaging about 16 weeks.]

   The percentage of patients with a Partial Response or Complete Response recorded from the start of the treatment until disease progression/recurrence by RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Progression-free Survival [Averaging about 16 weeks]

   Measures the length of time from the first day of therapy until Progressive Disease, death from any cause, or last patient contact. Disease Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

2. Overall Survival [Averaging about 47 weeks]

   Length of time from the first day of therapy to death from any cause or last patient contact

3. Disease Control Rate [The duration of study treatment, averaging about 16 weeks.]

   The percentage of patients with a Partial Response, a Complete Response, or Stable Disease during the study. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologic or cytologic diagnosis of adenocarcinoma non-small cell lung cancer

• Stage IV non-small cell lung cancer or recurrent disease which cannot be approached with curative intent.

• First-line treatment with a standard platinum doublet chemotherapy regimen (carboplatin or cisplatin at standard dosing plus one of the following drugs at standard dosing: paclitaxel, docetaxel, vinblastine, vinorelbine, pemetrexed, or etoposide). Patients who received platinum-based chemotherapy for localized lung cancer (either adjuvant chemotherapy following surgery or chemotherapy given in conjunction with definitive radiation) are eligible if their cancer has recurred within 6 months of platinum-based chemotherapy.

• Must have recovered from toxic effects of prior chemotherapy

• ECOG performance status of 0-1

• Life expectancy of at least 12 weeks

• Age 18 or greater

• Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as > 20 mm with conventional techniques or > 10 mm with spiral CT scanning).

• Patients with prior malignancies are allowed, provided they have been treated with curative intent and have no evidence of active disease.

• Patients must be capable of giving informed consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.

• Bilirubin < 1.5 mg/dL

• Patients must have adequate liver function: AST and ALT < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis

• Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3, Hemoglobin > 9.0g/dL and ANC > 1,500 cells/mm3

• Patients must have adequate renal function: creatinine <1.5 mg/dL

• Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment

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

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

Exclusion Criteria:

• Patients with EGFR or EML4-ALK mutations

• ECOG performance status >1

• Patients previously treated with gemcitabine or Abraxane

• Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Known HIV or Hepatitis C

• Untreated central nervous system metastases. Patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment.

• Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent

• Pregnant or breast-feeding patients, as chemotherapy is thought to present substantial risk to the fetus/infant. Men and women of reproductive potential may not participate in this study unless they have agreed to use an effective contraceptive method while in this study. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 3 months from the date of the last study drug administration

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Christine Ciunci, MD, Abramson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 9, 2019

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02303977
• Other Study ID Numbers: UPCC 21514
• First Posted: Dec 1, 2014
• Last Update Posted: Sep 29, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Adenocarcinoma; Adenocarcinoma of Lung; Gemcitabine; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
Period Title: Overall Study
STARTED	37
COMPLETED	37
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
Overall Participants	37
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 45.9%
>=65 years	20 54.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66
Sex: Female, Male (Count of Participants)
Female	22 59.5%
Male	15 40.5%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	37 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	The percentage of patients with a Partial Response or Complete Response recorded from the start of the treatment until disease progression/recurrence by RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Averaging about 16 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
Measure Participants	37
Number (95% Confidence Interval) [percentage of participants]	13.5 36.5%

2. Secondary Outcome

Title	Progression-free Survival
Description	Measures the length of time from the first day of therapy until Progressive Disease, death from any cause, or last patient contact. Disease Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Averaging about 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
Measure Participants	37
Median (95% Confidence Interval) [Months]	2.6

3. Secondary Outcome

Title	Overall Survival
Description	Length of time from the first day of therapy to death from any cause or last patient contact
Time Frame	Averaging about 47 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
Measure Participants	37
Median (95% Confidence Interval) [Months]	6.2

4. Secondary Outcome

Title	Disease Control Rate
Description	The percentage of patients with a Partial Response, a Complete Response, or Stable Disease during the study. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	The duration of study treatment, averaging about 16 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle. Abraxane Gemcitabine
Measure Participants	37
Number (95% Confidence Interval) [Percentage of participants]	59.5 160.8%

Adverse Events

Time Frame	Adverse events were assessed from the time of the initiation of study treatment, until 30 days after the end of study treatment, for an average of about 20 weeks. All-Cause Mortality was assessed from the time of study initiation until the death of the subject by any cause, up to approximately 47 weeks.
Arm/Group Title	Gemcitabine + Paciltaxel
Arm/Group Description	All patients were treated intravenously with albumin-bound paclitaxel at 100 mg/m2 plus gemcitabine at 1000 mg/m2 on days 1 and 8 of each three-week cycle.
All Cause Mortality
	Gemcitabine + Paciltaxel
	Affected / at Risk (%)	# Events
Total	36/37 (97.3%)
Serious Adverse Events
	Gemcitabine + Paciltaxel
	Affected / at Risk (%)	# Events
Total	22/37 (59.5%)
Blood and lymphatic system disorders
anemia	3/37 (8.1%)	3
Gastrointestinal disorders
Vomitting	4/37 (10.8%)	4
Diarrhea	1/37 (2.7%)	1
Nausea	2/37 (5.4%)	2
General disorders
Failure to thrive	1/37 (2.7%)	1
Infections and infestations
Lung Infection	5/37 (13.5%)	5
Sepsis	2/37 (5.4%)	2
ANC Decreased	4/37 (10.8%)	4
WBC decreased	1/37 (2.7%)	1
Soft Tissue Infection	2/37 (5.4%)	2
Metabolism and nutrition disorders
Dehydration	1/37 (2.7%)	1
Hyponatremia	1/37 (2.7%)	1
Hyperglycemia	1/37 (2.7%)	1
Nervous system disorders
Myelitis	1/37 (2.7%)	1
Tumor invasion of left brachial plexus	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/37 (5.4%)	2
Dyspnea	2/37 (5.4%)	2
Bronchopulmonary Hemorrhage	2/37 (5.4%)	2
Pneumonitis	2/37 (5.4%)	2
Respiratory Failure	2/37 (5.4%)	2
Hypoxia	1/37 (2.7%)	1
Vascular disorders
thromboembolic event	7/37 (18.9%)	7
Other (Not Including Serious) Adverse Events
	Gemcitabine + Paciltaxel
	Affected / at Risk (%)	# Events
Total	34/37 (91.9%)
Blood and lymphatic system disorders
Anemia	17/37 (45.9%)
White blood cell decreased	5/37 (13.5%)
Gastrointestinal disorders
Nausea	12/37 (32.4%)
Diarrhea	7/37 (18.9%)
Vomitting	7/37 (18.9%)
Constipation	4/37 (10.8%)
General disorders
Fatigue	19/37 (51.4%)
Fever	7/37 (18.9%)
Investigations
Neutrophil count decreased	10/37 (27%)
Platelet count decreased	6/37 (16.2%)
ALT increased	5/37 (13.5%)
AST Increased	4/37 (10.8%)
Metabolism and nutrition disorders
Anorexia	9/37 (24.3%)
Musculoskeletal and connective tissue disorders
Myalgia	4/37 (10.8%)
Nervous system disorders
Neuropathy	5/37 (13.5%)
Skin and subcutaneous tissue disorders
Alopecia	11/37 (29.7%)
Rash	5/37 (13.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.