Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01353625
Collaborator
(none)
118
Enrollment
17
Locations
1
Arm
118.6
Actual Duration (Months)
6.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.

Detailed Description

Latest amendment clarifies that Chronic Lymophocytic Leukemia (CLL) includes T-cell Prolymphocytic Leukemia (T-PLL). Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted.

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1a/1b, Multicenter, Open Label, Dosefinding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual Dna-pk and Tor Kinase Inhibitor, Cc-115, Administered Orally to Subjects With Advanced Solid Tumors and Hematologic Malignancies
Actual Study Start Date :
Apr 25, 2011
Actual Primary Completion Date :
Mar 12, 2021
Actual Study Completion Date :
Mar 12, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: CC-115

Drug: CC-115
Part A (actively recruiting): Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity). Part B: Optimal dose schedule is administered in 28-day cycles until disease progression.

Outcome Measures

Primary Outcome Measures

  1. Dose-Limiting Toxicity [Continuously for 28 days after starting treatment]

  2. Non-Tolerated Dose [Continuously for 28 days after starting treatment]

  3. Maximum Tolerated Dose [Continuously for 28 days after starting treatment]

  4. Maximum Observed Concentration in Plasma of CC-115 [Days 1, 2, 15, 16 of treatment]

  5. Area Under the Concentration-Time Curve for CC-115 [Days 1, 2, 15 and 16 of treatment]

  6. Time to Maximum Concentration of CC-115 [Days 1, 2, 15, and 16 of treatment]

  7. Terminal Half-Life for CC-115 [Days 1, 2, 15, and 16 of treatment]

  8. Apparent Total Body Clearance of CC-115 [Days 1, 2, 15 and 16 of treatment]

  9. Apparent Volume of Distribution of CC-115 [Days 1, 2, 15, and 16 of treatment]

  10. Accumulation Index of CC-115 [Days 1, 2, 15 and 16 of treatment]

Secondary Outcome Measures

  1. Pharmacodynamics [Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment]

    Phosphorylation inhibition determined by changes in the levels of multiple biomarkers including S6 and, 4EBP (for mTORC1), AKT (for mTORC2) and other appropriate biomarkers in circulating granulocytes and tumor tissue (when available).

  2. Anti-Tumor Efficacy [Every 2-3 months until proof of tumor progression]

    Tumor response rates using appropriate objective criteria for various malignancies

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma

  • Progressed or not tolerated standard therapy, and no further standard therapy is available

  • Archival and screening tumor biopsy

  • Eastern Cooperative Oncology Group Performance Status: 0 or 1

  • Adequate organ function

Exclusion Criteria:
  • Prior cancer-directed modalities or investigational drugs within 4 wks or 5 half lives, whichever is shorter

  • Symptomatic brain metastases (prior treatment and stable metastases are allowed)

  • Acute or chronic renal disease or pancreatitis

  • Diarrhea ≥ Grade 2, impaired gastrointestinal absorption

  • Impaired cardiac function

  • History of diabetes requiring treatment, glucose >126 mg/dL, Glycated hemoglobin (HbA1c) ≥6.5%

  • Peripheral neuropathy ≥ Grade 2

  • Known Human Immunodeficiency Virus (HIV) infection, chronic hepatitis B or C (unless associated with hepatocellular cancer)

  • Pregnant, inadequate contraception, breast feeding

  • Most concurrent second malignancies

  • Part B only: Prior treatment with agents targeting both mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Cedars-Sinai Medical CenterLos AngelesCaliforniaUnited States90048
2UCLALos AngelesCaliforniaUnited States90095
3University of California, San Francisco Comprehensive Cancer Center and Cancer Research InstitiuteSan FranciscoCaliforniaUnited States94115
4Moffitt Cancer CenterTampaFloridaUnited States33612
5University of Michigan Comprehensive Cancer CenterAnn ArborMichiganUnited States48109
6Henry Ford Medical Center - New Center OneDetroitMichiganUnited States48202
7Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10021
8Sarah Cannon Research Institute Drug Development UnitNashvilleTennesseeUnited States37203
9Mary Crowley Medical Research CenterDallasTexasUnited States75201
10The University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77303
11Gustave RoussyVillejuif CedexFrance94805
12Uniklinik KolnKoelnGermany50937
13Universitatsklinikum WurzburgWürzburgGermany97070
14Hospital Val d'HebronBarcelonaSpain08035
15Hospital Universitario Madrid SanchinarroMadridSpain28050
16Hospital de DonostiSan Sebastián (Guipuzcoa)Spain20014
17Hospital Virgen del RocioSevillaSpain41013

Sponsors and Collaborators

  • Celgene

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01353625
Other Study ID Numbers:
  • CC-115-ST-001
First Posted:
May 13, 2011
Last Update Posted:
Oct 5, 2021
Last Verified:
Sep 1, 2021

Study Results

No Results Posted as of Oct 5, 2021