Temsirolimus and Bryostatin 1 in Treating Patients With Unresectable or Metastatic Solid Tumors

May 1, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of Intravenous CCI-779 in Combination With Bryostatin-1 in Solid Tumors (10038414)

This phase I trial is studying the side effects and best dose of temsirolimus when given together with bryostatin 1 in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as temsirolimus and bryostatin 1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of temsirolimus when given together with bryostatin 1 in patients with unresectable or metastatic solid tumors.

II. Determine the dose-limiting toxic effects of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Correlate the extent and duration of inhibition of p70^S6kinase phosphorylation in peripheral blood mononuclear cells with tumor growth or reduction in these patients.

II. Correlate the phosphorylation total and phospho-AKT and total and phospho ribosomal S6 protein (indicators of mTOR activation) with antitumor effects of this regimen in these patients.

III. Correlate tumor expression of phospho-ERK1 and -ERK2 with antitumor effects of this regimen in these patients.

IV. Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of temsirolimus.

Patients receive bryostatin 1 IV over 1 hour on days 1, 8, 15, and 22 and temsirolimus IV over 30 minutes once on days 8, 15, and 22 during course 1. On subsequent courses patients receive bryostatin 1 and temsirolimus once on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed solid tumor, including melanoma or renal cell carcinoma

    • Metastatic or unresectable disease

      • Must have evidence of residual, recurrent, or metastatic disease by radiography

  • Measurable disease

    • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (CT scan, MRI, or x-ray) OR ≥ 10 mm by spiral CT scan
    • Must show clear evidence of disease progression within the lesion if the only site of measurable disease is within a previously irradiated volume
  • Standard curative or palliative measures do not exist OR are no longer effective
  • No history of or known brain metastases
  • Performance status - ECOG 0-1
  • At least 3 months
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin normal
  • Creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Fasting cholesterol ≤ 350 mg/dL*
  • Triglycerides ≤ 400 mg/dL*
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use effective contraception for ≥ 1 month before, during, and for ≥ 3 months after completion of study treatment (during and for ≥ 3 months after completion of study treatment for male patients)
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
  • No ongoing or active bacterial or viral infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No dementia or altered mental status that would preclude giving informed consent
  • No other uncontrolled illnesses
  • More than 3 weeks since prior immunotherapy
  • Prior biological therapy (e.g., interferon or interleukin 2, vaccine, antibody-based and tyrosine kinase inhibitors) allowed
  • No concurrent prophylactic hematopoietic colony-stimulating factors except for epoetin alfa
  • No prior cytotoxic chemotherapy
  • No prior bryostatin 1, temsirolimus, everolimus, or AP23573 for this malignancy
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No concurrent steroids except for topical or inhaled use
  • No other concurrent experimental agents
  • No prior radiotherapy to > 25% of bone marrow
  • More than 3 weeks since prior radiotherapy

  • More than 3 weeks since prior major surgery, including nephrectomy

    • Minor surgical procedures allowed
  • Recovered from prior therapy
  • More than 3 weeks since prior other anticancer investigational agents
  • Concurrent CYP3A4 inducers or inhibitors allowed provided patient has been on a stable dose for ≥ 1 week before study entry
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent antineoplastic agents or therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (bryostatin, temsirolimus)
Patients receive bryostatin 1 IV over 1 hour on days 1, 8, 15, and 22 and temsirolimus IV over 30 minutes once on days 8, 15, and 22 during course 1. On subsequent courses patients receive bryostatin 1 and temsirolimus once on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: temsirolimus
Given IV
Other Names:
  • Torisel
  • CCI-779
  • cell cycle inhibitor 779
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD of CCI-779 and Bryostatin-1 administered in combination, graded according to NCI Common Toxicity Criteria, Version 3.0
Time Frame: 28 days
A dose-limiting toxicity is defined as a toxicity that is >= grade 3 and drug-related.
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in sum of RECIST measurements
Time Frame: Baseline up to 30 days after completion of study treatment
Baseline up to 30 days after completion of study treatment
AKT activity, measured by immunohistochemistry (IHC), classified as none, weak, moderate, or strong
Time Frame: Up to 30 days after completion of study treatment
Up to 30 days after completion of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Gary Hudes, Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

June 2, 2005

First Submitted That Met QC Criteria

June 2, 2005

First Posted (Estimate)

June 3, 2005

Study Record Updates

Last Update Posted (Estimate)

May 3, 2013

Last Update Submitted That Met QC Criteria

May 1, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2011-01382
  • 04-037
  • FCCC-04037
  • NCI-5785
  • CDR0000432955

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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