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Adult Grade III Lymphomatoid GranulomatosisPhase 1NCT00891072

Gossypol, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

A Phase 1 study testing R-(-)-gossypol acetic acid, paclitaxel and carboplatin in people with Adult Grade III Lymphomatoid Granulomatosis and Adult Nasal Type Extranodal NK/T-cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 gossypol when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
R-(-)-gossypol acetic acid, paclitaxel and carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Jul 2009to Apr 2011
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

  • Patients must have histologically or cytologically confirmed malignancy that is metastatic and unresectable and for which standard curative or palliative measures do not exist or are no longer effective; patient may have previously treated or untreated disease
  • Patients may have had no more than nine months of previous marrow damaging cytotoxic chemotherapy; examples include but are not limited to: platinum agents cyclophosphamide, ifosfamide, BCNU, and mitomycin C; chemotherapy agents that are non-alkylators such as fluorouracil or taxanes will not be considered marrow damaging chemotherapy; patients must be at least 28 days from last prior chemotherapy or molecular therapy; at least six weeks from last chemotherapy if the regimen included BCNU or mitomycin C; it must be at least 2 weeks from last radiation therapy and less than a total of 30% of the bone marrow receiving radiation dose > 3000 cGy; in addition, patients may not have received previous high-dose therapy requiring hematopoietic stem cell transplantation nor can they have received anti-cancer treatments involving radioactive pharmaceuticals
  • Patients with non-Hodgkins lymphoma that is amenable to hematopoietic stem cell transplantation with curative intent may participate only if stem cell transplant is refused or is not indicated
  • ECOG performance status =< 2, Karnofsky ≥ 60%
  • Life expectancy of greater than 3 months
  • Absolute Neutrophil Count ≥ 1,500/uL
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  • Platelets ≥ 100,000/uL
  • Total bilirubin within normal institutional limits
  • AST (SGOT)/ALT (SGPT) =< 2.5 X institutional ULN
  • Creatinine within normal institutional limits OR a measured creatinine clearance by 24 hour urine collection greater than 60 mL/min; a calculated creatinine clearance by Cockcroft-Gault Formula is acceptable in lieu of a measured value
  • All Patients must have Measurable or Evaluable Disease per RECIST Criteria
  • 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) 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 with previously treated brain metastases who are clinically and radiographically stable or improved at least four weeks after completion of radiation therapy and are off steroids are eligible; an MRI of the brain or CT scan of the head with contrast must be performed at baseline for patients with history of and/or symptoms suspicious of brain metastases
  • Patients must sign informed consent

Who cannot join

  • Treatment with chemotherapy, hormonal agents (except LHRH agonists/antagonists) used for their anti-cancer activity, or biologic response modifiers within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Failure to recover fully (as judged by the investigator) from prior surgical procedures, or failure to recover from adverse events due to agents administered more than 4 weeks earlier
  • 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; use of erythropoietin stimulating agents and RBCs prior to study enrollment is allowed
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  • Neuropathy is a well described side effect of paclitaxel and carboplatin; patients may not have baseline peripheral neuropathy >= Grade 2
  • 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 within the last three months 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 affect safety or 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
  • 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
  • Patients with a myocardial infarction (MI) or cardiac (heart) surgery within the past 3 months

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

Official title: A Phase 1 Study of R-(-)-Gossypol (Ascenta's AT-101) in Combination With Paclitaxel and Carboplatin in Solid Tumors

This phase I trial is studying the side effects and best dose of gossypol when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Drugs used in chemotherapy, such as gossypol, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gossypol together with paclitaxel and carboplatin may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. The primary end point will be to determine the maximum tolerated dose of AT-101 with paclitaxel and carboplatin.

SECONDARY OBJECTIVES:

  1. To describe the toxicities associated with the combination of paclitaxel, carboplatin, and AT-101.

II. To evaluate the human pharmacokinetic disposition of AT-101 in the context of escalating doses.

III. To describe the pharmacokinetics of paclitaxel when given concurrently with AT-101.

IV. To evaluate for evidence of activity for the combination of paclitaxel, carboplatin and AT-101.

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

Patients receive oral R-(-)-gossypol acetic acid twice daily on days 1-3. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies by liquid chromatography/mass spectrometry.

After completion of study therapy, patients are followed for 4 weeks.

Being tested
R-(-)-gossypol acetic acid, paclitaxel, carboplatin, pharmacological study
Medical subject headings
Lymphoma, Extranodal NK-T-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, T-Cell, Peripheral, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

  • paclitaxelDrug

    Also called Anzatax, Asotax, TAX, Taxol

    Given IV

  • carboplatinDrug

    Also called Carboplat, CBDCA, JM-8, Paraplat

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00891072
Study groupRoleWhat they receive
TreatmentExperimentalPatients receive oral R-(-)-gossypol acetic acid twice daily on days 1-3. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: R-(-)-gossypol acetic acid; Drug: paclitaxel; Drug: carboplatin; Other: pharmacological study

What is being measured

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

  1. MTD, defined as the highest dose level below the maximally administered dose at which no more than 1 out of 6 patients experience DLT graded according to NCI CTCAE version 4.0

    Measured: Up to 21 days

Secondary outcomes (4)

  1. AT-101 level (bound and unbound)

    Samples will be analyzed by validated LC-MS techniques.

    Measured: Up to 4 weeks after completion of study treatment

  2. Paclitaxel level (bound and unbound)

    Samples will be analyzed by validated LC-MS techniques.

    Measured: Up to 4 weeks after completion of study treatment

  3. Pharmacokinetics of AT-101

    Pharmacokinetics will be determined by standard two-stage approaches using non-compartmental and compartmental modeling.

    Measured: Day 1 of courses 1 and 2 pre-AT-101 treatment and at 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, and 24 hours after AT-101 administration

  4. Pharmacokinetics of paclitaxel

    Pharmacokinetics will be determined by standard two-stage approaches using non-compartmental and compartmental modeling.

    Measured: Day 1 of courses 1 and 2 pre-AT-101 treatment and at 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, and 24 hours after AT-101 administration

Timeline

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

  1. First posted30 Apr 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionApr 2011
  4. Study completionApr 2011

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
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00891072
Sponsor's protocol ID
NCI-2012-03109
Other IDs
050905, U01CA132194, CDR0000640622
Status last verified
Jan 2013
First submitted
29 Apr 2009
Last updated
10 Jan 2013
Results posted
No

Publications

  • Stein MN, Goodin S, Gounder M, Gibbon D, Moss R, Portal D, Lindquist D, Zhao Y, Takebe N, Tan A, Aisner J, Lin H, Ready N, Mehnert JM. A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors. Invest New Drugs. 2020 Jun;38(3):855-865. doi: 10.1007/s10637-019-00807-2. Epub 2019 Aug 6.

    PubMed 31388792

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing R-(-)-gossypol acetic acid, paclitaxel and carboplatin in people with Adult Grade III Lymphomatoid Granulomatosis and Adult Nasal Type Extranodal NK/T-cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 14 inclusion and 14 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 10 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

MTD, defined as the highest dose level below the maximally administered dose at which no more than 1 out of 6 patients experience DLT graded according to NCI CTCAE version 4.0 (time frame: Up to 21 days). 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 NCT00891072, which also lists 1 linked publication.

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 10 Jan 2013.

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