Vandetanib, Carboplatin, and Paclitaxel in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer That Can Be Removed by Surgery

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00459121
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving vandetanib together with carboplatin and paclitaxel works in treating patients with stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin; Drug: paclitaxel; Drug: Zactima; Procedure: neoadjuvant therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the feasibility of neoadjuvant vandetanib in combination with carboplatin and paclitaxel in patients with resectable stage IB, II, or IIIA non-small cell lung cancer.

Secondary

• Assess the 30-day postoperative mortality rate in these patients.

• Assess the toxicity of this regimen in these patients.

• Determine the percentage of patients who complete all planned courses of therapy.

• Assess the clinical response rate in patients treated with this regimen.

• Assess the pathologic complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral vandetanib once daily on days 1-21. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 3 courses.

Patients undergo surgery at least 3 weeks after the last course of chemotherapy.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Feasibility and Safety of the Addition of ZD6474 (Zactima) to Carboplatin and Paclitaxel Administered Neo-Adjuvantly in Stage IB, II and T3, N1 Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Zactima, Paclitaxel, Carboplatin Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.

Drug: carboplatin; Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1; Other Names: Paraplatin ® ; Drug: paclitaxel; Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1.; Other Names: Taxol ® Onxal TM ; Drug: Zactima; Zactima- 100 mg orally daily, starting on day 1 of cycle 1.; Other Names: Caprelsa ZD6474 Vandetanib ; Procedure: neoadjuvant therapy; Neoadjuvant surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.; Other Names: R0 Resection

Outcome Measures

Primary Outcome Measures

1. Complete Resection (R0) Rate [Following three cycles of pre-operative zactima and carboplatin/paclitaxel]

Secondary Outcome Measures

1. Post-Operative Mortality Rate [at 30 days]

2. Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy [Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel]

   Serum chemistry includes Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT [AST], SGPT [ALT], sodium, laboratory tests should be done on a weekly basis for the first cycle. After the first cycle laboratory tests should be done within 72 hours of each dose of carboplatin/paclitaxel.

3. Assess the Clinical Response Rate of the Proposed Pre-operative Regimen [End of three cycles of treatment]

   Patients will undergo tumor evaluation when all of the three cycles have been completed unless the treating physician has concerns regarding tumor progression. If the patient has undergone tumor evaluation prior to the last cycle the patient will require repeat tumor assessment within 4 weeks of completion of the last cycle of therapy

4. Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen. [30 days post surgery]

   Evaluation of the number of patients who have no evidence of tumor in the resected tumor.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria:

• Stage IB or II disease

• T3, N0-1 disease (stage IIIA)

• Deemed a surgical candidate

• No prior lung cancer (NSCLC or small cell lung cancer)

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

• WBC ≥ 3,000/mm³

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

• Creatinine ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the investigator, would preclude study compliance

• No peripheral neuropathy ≥ grade 2

• No hemoptysis within the past 12 weeks

• No spontaneous bleeding within the past 12 weeks

• No clinically significant cardiac event (e.g., NYHA class II-IV heart disease, myocardial infarction) within the past 3 months

• No history of asymptomatic sustained ventricular tachycardia or arrhythmia that is symptomatic or requires treatment, including any of the following:

• Multifocal premature ventricular contractions

• Bigeminy

• Trigeminy

• Ventricular tachycardia

• Uncontrolled atrial fibrillation

• Atrial fibrillation controlled with medication allowed

• No history of QTc prolongation as a result from other medication that required discontinuation of that medication

• No congenital long QT syndrome or first-degree family relative with an unexplained death before the age of 40

• No left bundle branch block

• No QTc with Bazett's correction that is unmeasurable or QTc ≥ 480 milliseconds on screening ECG

• Patients with QTc ≥ 480 milliseconds on screening ECG may have ECG repeated twice

• Average QTc from the 3 screening ECG's must be < 480 milliseconds

• No uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg)

• No active diarrhea or active gastrointestinal disease that may affect the absorption of study drugs or ability to tolerate study drugs

• No other malignancy within the past 3 years except in situ cervical carcinoma or adequately treated basal cell or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since major surgery and recovered

• No prior carboplatin, paclitaxel, or vandetanib

• More than 30 days since prior investigational agents

• More than 2 weeks since prior and no concurrent drugs that induce CYP3A4 including, but not limited to, any of the following:

• Rifampin

• Phenytoin

• Carbamazepine

• Barbiturates

• Hypericum perforatum (St. John's wort)

• No medication that may cause QTc prolongation or induce torsades de pointes for 2 weeks prior to beginning study treatment, during, and for 2 weeks after completion of study treatment

• No concurrent combination antiretroviral treatment for HIV-positive patients

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Study Chair: Shirish M. Gadgeel, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Shirish M. Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00459121
• Other Study ID Numbers: CDR0000539273; P30CA022453; WSU-2006-122; WSU-011807MP2F; WSU-0612004427; ZENECA-IRUSZACT0029
• First Posted: Apr 11, 2007
• Last Update Posted: Mar 26, 2019
• Last Verified: Feb 1, 2013

• Keywords provided by Shirish M. Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute: stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage IIIA non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin

Study Results

Participant Flow

Recruitment Details	Unable to enroll patients in a timely fashion. The decision was made to close the study after consulting with AstraZeneca.
Pre-assignment Detail	Feasibility and safety.

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (0)
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Complete Resection (R0) Rate
Time Frame	Following three cycles of pre-operative zactima and carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

No analysis was completed only 2 patients enrolled, study closed due to slow accrual.

Arm/Group Title	Zactima+Carboplatin & Paclitaxel-assess Feasibility & Safety
Arm/Group Description	Study closed before an evaluable number of participants could be accrued. No summary of statistics will be collected for two participants, per the statistician.
Measure Participants	0

2. Secondary Outcome

Title	Post-Operative Mortality Rate
Time Frame	at 30 days

Outcome Measure Data

Analysis Population Description

No analysis was completed only 2 patients enrolled, study closed due to slow accrual.

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Measure Participants	0

3. Secondary Outcome

Title	Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy
Description	Serum chemistry includes Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT [AST], SGPT [ALT], sodium, laboratory tests should be done on a weekly basis for the first cycle. After the first cycle laboratory tests should be done within 72 hours of each dose of carboplatin/paclitaxel.
Time Frame	Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel

Outcome Measure Data

Analysis Population Description

No analysis was completed only 2 patients enrolled, study closed due to slow accrual.

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Measure Participants	0

4. Secondary Outcome

Title	Assess the Clinical Response Rate of the Proposed Pre-operative Regimen
Description	Patients will undergo tumor evaluation when all of the three cycles have been completed unless the treating physician has concerns regarding tumor progression. If the patient has undergone tumor evaluation prior to the last cycle the patient will require repeat tumor assessment within 4 weeks of completion of the last cycle of therapy
Time Frame	End of three cycles of treatment

Outcome Measure Data

Analysis Population Description

No analysis was completed only 2 patients enrolled, study closed due to slow accrual.

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Measure Participants	0

5. Secondary Outcome

Title	Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen.
Description	Evaluation of the number of patients who have no evidence of tumor in the resected tumor.
Time Frame	30 days post surgery

Outcome Measure Data

Analysis Population Description

No analysis was completed only 2 patients enrolled, study closed due to slow accrual.

Arm/Group Title	Zactima, Paclitaxel, Carboplatin
Arm/Group Description	Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle. Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Measure Participants	0

Adverse Events

Arm/Group Title	Zactima+Carboplatin & Paclitaxel-assess Feasibility & Safety
Arm/Group Description	Study closed before an evaluable number of participants could be accrued. No summary of statistics will be collected for two participants, per the statistician.
All Cause Mortality
	Zactima+Carboplatin & Paclitaxel-assess Feasibility & Safety
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zactima+Carboplatin & Paclitaxel-assess Feasibility & Safety
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Zactima+Carboplatin & Paclitaxel-assess Feasibility & Safety
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Decreased ANC	2/2 (100%)	2
Hyperglycemia	1/2 (50%)	2
Decreased WBC count	1/2 (50%)	1
Hypercalcemia	1/2 (50%)	1
Decreased hemoglobin	1/2 (50%)	1
Cardiac disorders
Sinus tachycardia	1/2 (50%)	1
Gastrointestinal disorders
Nausea	2/2 (100%)	2
Constipation	1/2 (50%)	1
Vomiting	1/2 (50%)	1
Diarrhea	1/2 (50%)	1
General disorders
Cough	1/2 (50%)	1
Fatigue	2/2 (100%)	2
Metabolism and nutrition disorders
Bicarbonate	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Myalgia	2/2 (100%)	2
Chills	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Rash	1/2 (50%)	1

Limitations/Caveats

This was a single center study. We did not accrue enough particpants in a timely fashion and a joint decision was made with AstraZeneca to terminate the study.

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.