Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC

NCT00544648 | Terminated Phase 1 Results DMC

• 3 other identifiers: VICC THO 0746P30CA068485VU-VICC-THO-0746
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) may make tumor cells more sensitive to radiation therapy. Giving nab-paclitaxel together with radiation therapy and carboplatin may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving nab-paclitaxel together with carboplatin and radiation therapy and to see how well it works in treating patients with stage III non-small-cell lung cancer that cannot be removed by surgery.

Conditions

Lung Cancer

Keywords

stage IV non-small cell lung cancer; stage IIIB non-small cell lung cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I)

  The highest dose in milligrams per meter of body surface squared (mg/m2) of nab-paclitaxel in combination with carboplatin while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of nab-paclitaxel in combination with carboplatin until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs per Common Toxicity Criteria v 3.0: recurring non-hematological (except esophagitis) \> Grade 2, non-hematological or esophagitis \> Grade 3 toxicities that are symptomatically unacceptable to patient and result in treatment delay for \> 2 weeks, persistent toxicity resulting in treatment delay for \> 2 weeks.

  7 weeks

• Progression-free Survival (Phase II)

  Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: \>= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions

  On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

Secondary Outcomes (7)

• Progression-free Survival (Phase I)

  On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

• Overall Survival (Phase I)

  On-study date to date of death from any cause (assessed up to 2 years)

• Response (Phase I)

  On-treatment date to date of progressive disease (assessed up to 2 years)

• Number of Patients With Each Worst Grade Toxicity (Phase I)

  On-study date to 30 days following final dose of study drug

• Overall Survival (Phase II)

  Time Frame: date on study to date of death from any cause or last known date alive

Other Outcomes (1)

• Secreted Protein Acidic and Rich in Cysteine (SPARC) Gene Expression

  On receipt of tumor tissue blocks

Study Arms (1)

Treatment

EXPERIMENTAL

nab-paclitaxel+ carboplatin + radiation

Drug: carboplatin; Drug: nab-paclitaxel; Radiation: Radiation therapy

Interventions

carboplatin DRUG

(AUC 2) through a vein over 30 minutes following nab-paclitaxel, once per week x 7 weeks

Also known as: Paraplatin

Treatment

nab-paclitaxel DRUG

Phase I: beginning at 40 mg/m2 through a vein over 30 minutes once per week x 7 weeks Phase II: Maximum tolerated dose through a vein over 30 minutes once per week x 7 weeks

Also known as: paclitaxel albumin-stabilized nanoparticle formulation, Abraxane

Treatment

Radiation therapy RADIATION

3D conformal radiotherapy or Intensity-Modulated Radiation Therapy (IMRT), 2.0 Gy per day x 5 days per week for 33 days during Weeks 1-7 ; Total Dose = 66 Gy

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must voluntarily sign and date an informed consent before the initiation of any study procedures
• Patients must have non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion
• Patients must not have received any prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC
• Patients must have at least one site of unidirectionally measurable disease as defined by Response Evaluation in Solid Tumors (RECIST) criteria
• Patients must be ≥ 3 weeks from a formal exploratory thoracotomy
• Patients must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry
• Patients must be ≥ 18 years of age
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Women of childbearing potential must have a negative baseline serum pregnancy or a negative urine pregnancy test within 7 days prior to Week 1, Day 1 and must not be breast feeding.
• Women of childbearing potential and men with a sexual partner of child bearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy.
• Patients must have adequate hepatic, renal, lung and bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥1,500/mm3
• Hemoglobin ≥ 9.0 gm/dL
• Serum Creatinine ≤1.5mg/dl
• Platelets \> 100,000/mm3

You may not qualify if:

• Known hypersensitivity to carboplatin or nab-paclitaxel
• Peripheral neuropathy Grade ≥ 2
• Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC
• Previous chemotherapy or radiation therapy to the chest
• Any concomitant malignancy or brain metastasis
• Any uncontrolled, clinically significant medical or psychiatric disorder
• Pregnant or nursing women
• A greater than or equal to 10% weight loss over the past 3 months

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Purchase Cancer Group - Paducah

Paducah, Kentucky, 42002, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97201, United States

Location

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, 37403, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Related Publications (1)

• Lammers PE, Lu B, Horn L, Shyr Y, Keedy V. nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer. Oncologist. 2015 May;20(5):491-2. doi: 10.1634/theoncologist.2015-0030. Epub 2015 Apr 6.

  PMID: 25845992 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; 130-nm albumin-bound paclitaxel; Taxes; Albumin-Bound Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics

Limitations and Caveats

This Phase I/II study progressed into Phase II, but terminated shortly thereafter due to lack of funding.

Results Point of Contact

• Title: Vicki Keedy, MD
• Organization: Vanderbilt-Ingram Cancer Center

vicki.keedy@vanderbilt.edu

615-936-3524

Study Officials

• Vicki Keedy, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Sarcoma Program; Medical Director, Clinical Trials Shared Resource; Medical Oncologist

Study Record Dates

• First Submitted: October 13, 2007
• First Posted: October 16, 2007
• Study Start: November 1, 2007
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 9, 2014
• Results First Posted: June 9, 2014

Record last verified: 2014-05

Locations

US (6)