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Extensive Stage Small Cell Lung CancerPhase 1NCT00544596

R-(-)-Gossypol Acetic Acid, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer

A Phase 1 study testing R-(-)-gossypol acetic acid, cisplatin and etoposide in people with Extensive Stage Small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of R-(-)-gossypol acetic acid when given together with cisplatin and etoposide in treating patients with advanced solid tumors or extensive stage small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
R-(-)-gossypol acetic acid, cisplatin and etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
4 sitesUnited States
Study dates
Sep 2007to Jul 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In the dose-escalation cohorts: patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; in the MTD expansion cohort: patients must have histologically or cytologically confirmed extensive-stage small cell lung cancer
  • Patients must not have received prior therapy that inhibits the B-cell lymphoma 2 (Bcl-2) family
  • Patients with small cell lung cancer may have received prior prophylactic cranial irradiation
  • Prior whole brain radiotherapy allowed for patients with brain metastases provided they have stable/improved lesions for at least 1 month following treatment, no neurological symptoms and not require corticosteroids; an magnetic resonance imaging (MRI) of the brain or computed tomography (CT) scan of the head must be performed at baseline if patient has a history of brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
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  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Serum creatinine < 1.5 x institutional upper limit of normal OR
  • Creatinine clearance >= 45 mL/min/1.73 m^2, as calculated by Cockroft-Gault formula, for patients with creatinine levels above institutional normal; a 24 hour urine collection and creatinine clearance can be measured if indicated
  • The effects of AT-101 on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least one month following the last dose of AT-101; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients should display the ability to understand and the willingness to sign a written informed consent document
  • Female patients of child bearing potential must not be pregnant
  • Patients must have measurable or evaluable disease

Who cannot join

  • Patients without small cell lung cancer who have had chemotherapy, radiotherapy or hormonal therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (=< grade 1) from clinically significant adverse events due to agents administered more than 4 weeks earlier; prior treatment with a platinum-based chemotherapy regimen in combination with thoracic radiation therapy is allowed for patients with ES-SCLC provided that recurrence of the SCLC occurred more than 6 months from definitive therapy for limited-stage small cell lung cancer; no other prior chemotherapy is allowed for the patients with ES-SCLC
  • Failure to recover fully (as judged by the investigator) from prior surgical procedures
  • Concurrent treatment with an investigational agent other than the investigational agent(s) used in this study OR treatment within 4 weeks of study entry with any investigational agent(s) or device(s)
  • Any prior use of racemic gossypol or AT-101
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AT-101 or other agents used in study
  • Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry; if patient requires routine use of erythropoietin, eligibility at investigator discretion
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  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain AT-101 tablets
  • Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because the effects of AT-101 on the developing human fetus are unknown, but could potentially include teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AT-101, breastfeeding should be discontinued if the mother is treated with AT-101; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AT-101 or other agents used in this study; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients with > grade 2 symptomatic hypercalcemia (based on investigator discretion)

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Gundersen Lutheran

    La Crosse, Wisconsin, 54601

  • UW Health Oncology - 1 South Park

    Madison, Wisconsin, 53715

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Sanford Cancer Center-Oncology Clinic

    Sioux Falls, South Dakota, 57104

Other trials in United States

About this study

Official title: A Phase 1 Study of R-(-)-Gossypol (AT-101) in Combination With Cisplatin and Etoposide in Patients With Advanced Solid Tumors and Extensive-Stage Small Cell Lung Cancer

This phase I trial is studying the side effects and best dose of R-(-)-gossypol acetic acid when given together with cisplatin and etoposide in treating patients with advanced solid tumors or extensive stage small cell lung cancer. R-(-)-gossypol acetic acid may stop the growth of cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving R-(-)-gossypol acetic acid together with combination chemotherapy may help kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of AT-101 (R-(-)-gossypol) when combined with cisplatin and etoposide in patients with advanced, refractory solid tumors and/or extensive stage small cell lung cancer (ES-SCLC). In addition, to determine the MTD or RP2D of AT-101 when combined with cisplatin, etoposide, and Neulasta.

II. To evaluate the toxicity and tolerability of AT-101 in combination with cisplatin and etoposide in patients with advanced, refractory solid tumors and/or ES-SCLC. In addition, evaluate the toxicity and tolerability of AT-101 with cisplatin, etoposide, and Neulasta.

III. To evaluate the antitumor activity of this combination per tumor measurements using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacokinetics of AT-101 as a single agent and in combination with cisplatin and etoposide in plasma.

II. To perform pharmacodynamic studies (genotyping of drug metabolizing enzymes, gene expression, and proteomics of drug-related pathways) on archived blood samples from patients treated with AT-101 in combination with cisplatin and etoposide.

OUTLINE: This is a dose-escalation study of R-(-)-gossypol.

Patients receive oral R-(-)-gossypol twice daily on days 1-3, cisplatin intravenously (IV) over 60 minutes on day 1*, and etoposide IV over 30 minutes on days 1*-3. Treatment repeats every 21 days for up to 6 courses during the dose escalation and 4 courses in the expanded extensive stage small cell lung cancer cohort, in the absence of disease progression or unacceptable toxicity.

Blood samples are collected on day 1 of courses 1 and 2 for pharmacokinetic analysis, biomarker assays, and correlative studies.

After completion of study treatment, patients are followed for 30 days.

[Note: *Cisplatin and etoposide will be started on day 2 during course 1; they will be given on day 1 during all subsequent courses.]

Being tested
R-(-)-gossypol acetic acid, cisplatin, etoposide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • R-(-)-gossypol acetic acidDrug

    Also called AT-101

    Given orally

  • cisplatinDrug

    Also called CACP, CDDP, CPDD, DDP

    Given IV

  • etoposideDrug

    Also called EPEG, VP-16, VP-16-213

    Given IV

Study groups in NCT00544596
Study groupRoleWhat they receive
Treatment (R-(-)-gossypol acetic acid, cisplatin, etoposide)ExperimentalPatients receive oral R-(-)-gossypol twice daily on days 1-3, cisplatin IV over 60 minutes on day 1*, and etoposide IV over 30 minutes on days 1*-3. Treatment repeats every 21 days for up to 6 courses during the dose escalation and 4 courses in the expanded extensive stage small cell lung cancer cohort, in the absence of disease progression or unacceptable toxicity. Blood samples are collected on day 1 of courses 1 and 2 for pharmacokinetic analysis, biomarker assays, and correlative studies. After completion of study treatment, patients are followed for 30 days. [Note: *Cisplatin and etoposide will be started on day 2 during course 1; they will be given on day 1 during all subsequent courses.]
Receives: Drug: R-(-)-gossypol acetic acid; Drug: cisplatin; Drug: etoposide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity and tolerability of R-(-)-gossypol acetic acid in combination with cisplatin and etoposide in terms of types and severities by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

    The 95% confidence interval will be obtained.

    Measured: Assessed up to 30 days after completion of study treatment

  2. Response as assessed by RECIST criteria

    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. A 95% confidence interval of the overall response rate will be constructed.

    Measured: Assessed up to 30 days after completion of study treatment

Secondary outcomes (1)

  1. Pharmacokinetics of R-(-)-gossypol acetic acid in combination with cisplatin and etoposide

    Summarized by dose level with simple summary statistics: means, medians, ranges, and standard deviations.

    Measured: Days 1 and 2 of courses 1 and 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionJul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00544596
Sponsor's protocol ID
NCI-2009-00273
Other IDs
NCI-2009-00273, CO07901, 2007-0145, CDR0000570006, CO 07901, 8062, P30CA014520, U01CA062491
Status last verified
Jun 2012
First submitted
13 Oct 2007
Last updated
2 Apr 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing R-(-)-gossypol acetic acid, cisplatin and etoposide in people with Extensive Stage Small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity and tolerability of R-(-)-gossypol acetic acid in combination with cisplatin and etoposide in terms of types and severities by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (time frame: Assessed up to 30 days after completion of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00544596.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2014.

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