Sunitinib Maintenance Therapy After Induction Platinum-Based Chemotherapy in Patients With ES-SCLC

• ClinicalTrials.gov Identifier: NCT00616109
• Recruitment Status: Completed
• First Posted: February 15, 2008
• Results First Posted: April 21, 2014
• Last Update Posted: April 21, 2014
• Sponsor: University of Michigan Rogel Cancer Center
• Information provided by (Responsible Party): Gregory Kalemkerian. M.D., University of Michigan Rogel Cancer Center

Study Description

Brief Summary:

The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.

Condition or disease	Intervention/treatment	Phase
Extensive-Stage Small Cell Lung Cancer	Drug: sunitinib	Phase 2

Detailed Description:

Despite a high initial response rate, all patients with extensive-stage small cell lung cancer treated with standard chemotherapy will develop disease progression, usually within one year of initial treatment. Therefore, prolonging progression-free survival in this disease is meaningful for clinical trials exploring agents such as sunitinib. Sunitinib is a drug that inhibits the biological pathway responsible for the growth and spread of cancer cells. For this reason, we believe that sunitinib maintenance therapy will delay or prevent recurrence and prolong survival.

The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Sunitinib (Sutent, SU11248) Maintenance Therapy After Induction Platinum-Based Chemotherapy in Patients With Extensive-Stage Small Cell Lung Cancer
• Study Start Date: September 2007
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: January 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: Maintenance Sunitinib; Main interventional arm of study. Subjects who received maintenance sunitinib experimentally on this study were from a population of (consenting) patients with histologically or cytologically documented Extensive-State Small Cell Lung Cancer (ES-SCLC) who did not progress (were classified as Complete Response or "CR", Partial Response or "PR", or Stable Disease or "SD") after an induction chemotherapy (Cisplatin and etoposide)

Drug: sunitinib; Sunitinib will be given at 50 mg/day as a single agent for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.; Other Name: Sutent

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival Rate [ Time Frame: 4 Months Post Treatment ]
   The proportion of patients who are progression-free at 4 months after starting sunitinib.

Secondary Outcome Measures :

1. Median Overall Survival [ Time Frame: up to 4 months post treatment ]
   Survival will be defined as the time from the first day of therapy to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. Survival for induction therapy will be calculated from day 1 of first cycle of chemotherapy. Survival for post-induction therapy will be calculated from the date the patient starts sunitinib.
2. Percent of Patients With an Objective Response [ Time Frame: 12 weeks (2 cycles) ]
   Scans were performed every 2 cycles to evaluate for response/progression. Response was assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Patients would be considered to have an objective response if they experience CR (Complete Response - Disappearance of all clinical and radiological evidence of target lesions and/or non-target lesions) or PR (Partial Response - A 30% or greater decrease in the sum of LD of all lesions in reference to the baseline sum LD).
3. Number of Patients That Discontinue Drug Due to Toxicity [ Time Frame: 20 weeks ]

   Tolerability of Sunitinib will be evaluated by looking at the number of participants who discontinue drug due to toxicity. Toxicity was graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v.3.0.

   In the event of any CTC, version 3.0 drug-related grade 3 or 4 non-hematologic or grade 4 hematologic adverse event(s), drug should be held until the toxicity resolves to < grade 1 and then the drug should be restarted at a one dose-level reduction.

   Recovery to acceptable levels of toxicity must occur within 4 weeks to allow continuation in the study.

   No more than 2 dose reductions are permitted for any patient. If further dose reduction is required, the patient must be removed from the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed extensive-stage SCLC. Extensive-stage is defined as disease that extends beyond one hemithorax and regional lymph nodes (ipsilateral or contralateral hilar, mediastinal, or supraclavicular lymph nodes), or with cytologically positive pleural effusion.
• Patients who have completed platinum-based chemotherapy and demonstrated a complete response, partial response, or stable disease can be registered on the trial. A maximum of 4 cycles of induction chemotherapy is allowed. Patients must begin therapy within 28-42 days after day 1 of the 4th cycle of induction therapy and within 28 days of scans demonstrating stable disease or better. Prior palliative radiation therapy will be allowed as long as radiation was completed at least 1 week before starting protocol therapy.
• Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade 1.
• Age * 18 years with Southwest Oncology Group (SWOG) performance status of 0,1 or 2 (Appendix 2).
• Adequate organ function as evidenced by the laboratory values listed in the protocol

Exclusion Criteria:

• Symptomatic or untreated brain or leptomeningeal metastases. Treated patients should be neurologically stable for at least 2 weeks after completion of appropriate therapy without the use of steroids. Patients currently on steroids are ineligible.
• More than 4 cycles of induction chemotherapy. Patients will be eligible for if they have completed at least 2 cycles of platinum-based induction chemotherapy and they have exhibited a complete or partial response to therapy. Patients who have received less than 4 cycles of induction chemotherapy and have less than a partial response will not be eligible.
• NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
• History of gross hemoptysis due to lung cancer.
• Previous or concurrent malignancies, with the exception of adequately treated squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any other malignancy treated and in clinical remission for more than 3 years.
• Major surgery or within 4 weeks of starting study treatment.
• Any history of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Ongoing cardiac dysrhythmias
• Hypertension that cannot be controlled by medications
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
• Therapeutic anticoagulation with warfarin or heparin.
• Serious concomitant medical illness, including, but not limited to, uncontrolled angina, myocardial infarction and/or stroke within 3 months, or HIV infection.
• Acute or chronic liver disease
• History of dementia, active psychiatric disorder or any other condition, considered by the treating physician to impair the patient's ability to take oral pills on a daily basis or comply with the protocol requirements.
• Pregnant or lactating females.
• Use of agents with proarrhythmic potential is not permitted during the study.

Contacts and Locations

Locations

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Gregory Kalemkerian, MD; University of Michigan Rogel Cancer Center

More Information

Publications of Results:

Schneider BJ, Gadgeel SM, Ramnath N, Wozniak AJ, Dy GK, Daignault S, Kalemkerian GP. Phase II trial of sunitinib maintenance therapy after platinum-based chemotherapy in patients with extensive-stage small cell lung cancer. J Thorac Oncol. 2011 Jun;6(6):1117-20. doi: 10.1097/JTO.0b013e31821529c3.

• Responsible Party: Gregory Kalemkerian. M.D., Professor of Internal Medicine, University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00616109
• Other Study ID Numbers: UMCC 2007.034; HUM12046 ( Other Identifier: IRBMED (University of Michigan Medical School IRB) )
• First Posted: February 15, 2008
• Results First Posted: April 21, 2014
• Last Update Posted: April 21, 2014
• Last Verified: March 2014

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Sunitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action