NCT00891072|CompletedPhase 1

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

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

National Cancer Institute (NCI)ClinicalTrials.gov

Compare

4 other identifiers

NCI-2012-03109050905U01CA132194CDR0000640622

Study Type

interventional

Target

Locations

1 country

Sites

Timeline

RegisteredApr 2009

StartedJul 2009

CompletionApr 2011

Brief 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. 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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1

Timeline

Completed

Started Jul 2009

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.8 years study duration

First Submitted

Initial submission to the registry

April 29, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

April 30, 2009

Completed

2 months until next milestone

Study Start

First participant enrolled

July 1, 2009

Completed

1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2011

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed

Last Updated

January 10, 2013

Status Verified

January 1, 2013

Enrollment Period

1.8 years

First QC Date

April 29, 2009

Last Update Submit

January 9, 2013

Conditions

Outcome Measures

Primary Outcomes (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
Up to 21 days

Secondary Outcomes (4)

AT-101 level (bound and unbound)
Up to 4 weeks after completion of study treatment
Paclitaxel level (bound and unbound)
Up to 4 weeks after completion of study treatment
Pharmacokinetics of AT-101
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
Pharmacokinetics of paclitaxel
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

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: R-(-)-gossypol acetic acidDrug: paclitaxelDrug: carboplatinOther: pharmacological study

Interventions

R-(-)-gossypol acetic acidDRUG

Given orally

Also known as: AT-101

Treatment

paclitaxelDRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Treatment

carboplatinDRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Treatment

pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies

Treatment

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
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

You may not qualify if:

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
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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (1)

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Related Publications (1)

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.
PMID: 31388792DERIVED

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-CellLymphoma, B-Cell, Marginal ZoneLymphoma, T-Cell, PeripheralBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom Macroglobulinemia

Interventions

gossypol acetic acidPaclitaxelTaxesCarboplatin

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoma, B-CellLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemiaHematologic DiseasesLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesEconomicsHealth Care Economics and OrganizationsCoordination Complexes

Study Officials

Mark Stein
Rutgers Cancer Institute of New Jersey
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 1
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: NIH
Responsible Party: SPONSOR

Study Record Dates

First Submitted

April 29, 2009

First Posted

April 30, 2009

Study Start

July 1, 2009

Primary Completion

April 1, 2011

Study Completion

April 1, 2011

Last Updated

January 10, 2013

Record last verified: 2013-01

Locations

US(1)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (4)

Study Arms (1)

Treatment

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (1)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations