Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Palbociclib

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Closed to accrual 09/01/2016

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, participants may be eligible to re-register to Arm III.

Closed to accrual 12/18/2015

Participants in Arm II eligible for re-registration receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Closed to accrual 09/01/2016

Given IV (arm II closed to accrual 12/18/2015)

Laboratory Biomarker Analysis

Vassiliki Papadimitrakopoulou

This phase II/III trial studies how well palbociclib works in treating cell cycle gene alteration positive patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for cell cycle gene alterations which can cause tumor cells to grow more quickly. Palbociclib may slow cell cycle progression and may be able to shrink tumors.

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the Phase III component by evaluating the objective response rate (ORR) for cell cycle gene alteration positive patients registered to S1400C treated with palbociclib. (Phase II) II. If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized Phase III trial. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression-free survival (IA-PFS) and overall survival (OS) of cell cycle gene alteration-positive patients treated with palbociclib. (Phase II) II. To evaluate the duration of response (DoR) among cell cycle gene alteration positive patients treated with palbociclib who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II) III. To evaluate the frequency and severity of toxicities associated with palbociclib. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to palbociclib beyond the chosen biomarker for biomarker-driven sub-studies.

II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung.

OUTLINE: As of 09/01/2016, all arms are closed to accrual.

ARM I (CLOSED TO ACCRUAL 09/01/2016): Patients receive palbociclib orally (PO) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.

ARM III (CLOSED TO ACCRUAL 09/01/2016): Patients in Arm II eligible for re-registration receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer

A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

Screen success rate is defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy.

Treatment arm randomization acceptance rate within each treatment arm of each randomized sub-study is defined as the ratio of the number of patients who receive any protocol treatment over the number that are randomized to that sub-study treatment arm.

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with palbociclib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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

It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a complete or partial response.

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.

It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration until death due to any cause.

It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.

It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment

Adverse Events (AEs) are reported per CTCAE Version 5.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment

National Cancer Institute (NCI)

SWOG Cancer Research Network

41 participants were assessed for AEs: 32 on palbociclib and 10 on docetaxel arm. 1 participant that was re-registered from the docetaxel arm to receive palbociclib after progression was assessed for AEs in both arms.

Adverse Events (AEs) are reported per CTCAE Version 5.0

Participants receive palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Palbociclib: Given PO

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Palbociclib.

Given IV (arm II closed to accrual 12/18/2015) Other Names: •Docecad

* Docetaxel
* RP56976
* Taxotere
* Taxotere Injection Concentrate

Laboratory Biomarker Analysis Correlative studies

Participants receive Palbociclib PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Palbociclib: Given PO

Patients receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Palbociclib.

Given IV (arm II closed to accrual 12/18/2015) Other Names: •Docecad

* Docetaxel
* RP56976
* Taxotere
* Taxotere Injection Concentrate

Laboratory Biomarker Analysis Correlative studies

Total

Age, Continuous

Sex: Female, Male

Asian

Black

Native American

White

Hispanic

Race/Ethnicity, Customized

Participants were graded according to the Zubrod Performance Status Scale.

0 - Fully active, able to carry out on all pre-disease performance without restriction.

1. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work.
2. - Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.

Performance status

Docetaxel arm closed before data were collected

Number of prior lines of therapy

Current smoker

Former smoker

Never-smoker

Smoking status

Present

Absent

Brain metastases

Lung Committee Statistician

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)

Evaluable and eligible participants that achieved complete or partial response. 1 participant died without evidence of progression at 12 months.

Duration of Response Among Participants Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1

Overall Survival With Investigational Therapy

Progression-free Survival With Palbociclib.

Anemia

Anorexia

Aspartate aminotransferase increased

Dyspnea

Fatigue

Febrile neutropenia

Generalized muscle weakness

Hyperglycemia

Hyponatremia

Hypotension

Lung infection

Lymphocyte count decreased

Neoplasms benign, malignant & unspecified-Other

Neutrophil count decreased

Platelet count decreased

White blood cell decreased

Participants who received at least one dose of palbociclib treatment.

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Screen Success Rate, Monitored by the Percentage of Screened Patients That Register to a Therapeutic Sub-study

Treatment Arm Randomization Acceptance Rate, Monitored by the Percentage of Patients That Receive at Least One Dose of the Treatment They Are Randomized to

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer	NCT02785939	CCND1 Gene Ampl... CCND2 Gene Ampl... CCND3 Gene Ampl... CDK4 Gene Ampli... Recurrent Squam... Stage IV Squamo...	Docetaxel Laboratory Biom... Palbociclib	18 Years -	SWOG Cancer Research Network
Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer	NCT02785939	CCND1 Gene Ampl... CCND2 Gene Ampl... CCND3 Gene Ampl... CDK4 Gene Ampli... Recurrent Squam... Stage IV Squamo...	Docetaxel Laboratory Biom... Palbociclib	18 Years -	SWOG Cancer Research Network
Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer	NCT02785939	CCND1 Gene Ampl... CCND2 Gene Ampl... CCND3 Gene Ampl... CDK4 Gene Ampli... Recurrent Squam... Stage IV Squamo...	Docetaxel Laboratory Biom... Palbociclib	18 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for ccnd1 gene amplification