Trial record 2 of 6 for:    rectal cancer | Open Studies | Interventional Studies | United States, Ohio | Other

CB-839 + Capecitabine in Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2016 by Case Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02861300
First received: August 5, 2016
Last updated: August 9, 2016
Last verified: August 2016
  Purpose
This study has two portions. The main goal of the Phase I portion of this research study is to see what doses of CB-839 and capecitabine can safely be given to patients without having too many side effects. Other purposes of this research study will be to determine what side effects are seen with this combination of medicines. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment.

Condition Intervention Phase
Colorectal Cancer
Colon Cancer
Rectal Cancer
Solid Tumor
Drug: CB-839
Drug: Capecitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of CB-839 and Capecitabine in Patients With Advanced Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • PHASE 1: Recommended dose for phase II study [ Time Frame: At least 21 days of treatment ] [ Designated as safety issue: No ]
    The Phase I study has been designed to define the recommended phase II dose of CB-839 and capecitabine. A traditional 3+3 dose escalation design will be adopted. Nine to twenty-four patients are expected to be enrolled, depending on the number of dose escalations and assuming that a total of 6 patients will be treated at the final recommended phase II dose level. Patients who complete the first 21 day treatment cycle of CB-839 and capecitabine chemotherapy will be included in the analysis.

  • PHASE 2: Number of patients with response to treatment [ Time Frame: Up to 18 months after beginning treatment ] [ Designated as safety issue: No ]

    In the phase II component of this study, the primary endpoint is response rate. Response rate will be determined using RECIST criteria.

    RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.



Secondary Outcome Measures:
  • PHASE 1: proportion of patient who respond to treatment [ Time Frame: At least 21 days of treatment ] [ Designated as safety issue: No ]

    Response rate will be determined using RECIST criteria.

    RECIST response categories: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.



Estimated Enrollment: 47
Study Start Date: August 2016
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CB-839 + capecitabine
Patients will receive CB-839 orally twice daily for 21 days (continuous administration) and capecitabine orally twice daily for 14/21 days. In the phase I portion of the study, patients will receive escalating doses of CB-839 and capecitabine and will have day 15 blood samples drawn and archived for as needed assessment of CB-839 pharmacokinetics. In the phase II portion of the study, patients will receiving CB-839 and capecitabine at doses determined in the phase II portion of the study. They will also undergo pre-treatment and post-treatment blood samples and tissue biopsies for evaluation of pharmacodynamic biomarkers.
Drug: CB-839
Patients will receive CB-839 orally twice daily during each cycle. Each cycle will be 21 days long. Disease assessment will occur after cycle 3.
Drug: Capecitabine
capecitabine will be given orally twice daily for 14-21 days of cycles. Each cycle will be 21 days long. Disease assessment will occur after cycle 3.
Other Name: Xeloda

Detailed Description:

Phase I Primary Objective:

To determine the safety, tolerability and recommended phase II dose (RP2D) of combination CB-839 and capecitabine chemotherapy in patients with advanced solid tumors for whom there are no remaining treatment options or for whom capecitabine is an acceptable therapy.

Phase II Primary Objective:

To determine the response rate of combination CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancers who are refractory to fluoropyrimidine therapy.

Phase I Secondary Objectives:

To determine the dose-limiting toxicities and maximum tolerated dose of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom capecitabine is an acceptable therapy.

To determine the antitumor response as assessed by RECIST criteria of combination therapy with CB-839 and capecitabine in patients with advanced solid tumors for whom there are no remaining treatment options or for whom capecitabine is an acceptable therapy.

Phase II Secondary Objectives:

To determine the progression free survival following treatment with CB-839 and capecitabine chemotherapy in patients with metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.

To determine the overall survival following treatment with CB-839 and capecitabine chemotherapy in patients who have metastatic PIK3CA mutant colorectal cancer and are refractory to fluoropyrimidine therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Phase I

    • Patients must have an advanced solid tumors for whom there are no remaining treatment options or colorectal patients who have progressed on front-line fluoropyrimidine containing therapy.
    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
    • Patients must have normal organ and marrow function as defined below:

      • Hemoglobin ≥ 9.0 g/dl
      • Leukocytes ≥ 3,000/mcL
      • Absolute neutrophil count ≥ 1,500/mcL
      • Platelet count ≥ 100,000/mcL
      • Serum creatinine ≤ 1.5 X institutional upper limit of normal
      • Total bilirubin ≤ 1.5mg/dL
      • Aspartate Aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 X institutional upper limit of normal
      • Alanine Aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
    • Patients must be able to swallow pills.
    • Patients must have the ability to understand and the willingness to sign a written informed consent document.
    • Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential.
  • Phase II

    • Patients must have histologically or cytologically confirmed, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutant metastatic colorectal cancer. PIK3CA status must be confirmed by tumor sequencing.
    • Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria that is amenable to biopsy and be willing to undergo pre- and post-treatment tumor biopsies. Lesions to be biopsied do not have to be those used for measurement.
    • Patients must have received and progressed on fluoropyrimidine or fluoropyrimidine based therapy. Receipt of prior oxaliplatin, irinotecan or regorafenib therapy is not required.
    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    • Patients must have normal organ and marrow function as defined below:

      • Hemoglobin ≥ 9.0 g/dl
      • Leukocytes ≥ 3,000/mcL
      • Absolute neutrophil count ≥ 1,500/mcL
      • Platelet count ≥ 100,000/mcL
      • Serum creatinine within normal institutional limits
      • Total bilirubin ≤ 1.5 mg/dL
      • AST (SGOT) ≤ 2.5 X institutional upper limit of normal
      • ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
    • Patients must be able to swallow pills.
    • Patients must have the ability to understand and the willingness to sign a written informed consent document.
    • Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential.

Exclusion Criteria:

  • Both Phase I and Phase II

    • Patients with ongoing toxicities > grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) Version 4.0 (excluding alopecia) due to prior anti-cancer therapy.
    • Patients receiving any other investigational agents or whom have received recent treatment for colorectal cancer (radiation within the previous two weeks, chemotherapy or investigational therapy within the previous four weeks).
    • Patients with untreated brain metastases/central nervous system disease will be excluded due to their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
    • Patients with a history of allergic reactions attributed to or intolerance to compounds of similar chemical or biologic composition to either CB-839 or capecitabine. If capecitabine has been received previously, must have tolerated at least an equivalent dose to the dose to be administered at their assigned dose level.
    • Patients who are unable to swallow pills or who have undergone surgery that prohibits the absorption of pills in the stomach.
    • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or myocardial infarction within prior 6 months, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
    • Patients who are pregnant or breastfeeding will be excluded from the study due to the potential teratogenic or abortifacient effects that may results from CB-839 and/or capecitabine. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CB-839 and/or capecitabine, breastfeeding should be discontinued if the mother is treated with CB-839 and/or capecitabine. These potential risks may also apply to other agents used in this study.
    • Patients known to be HIV positive who are not receiving anti-retroviral therapy will be excluded due to the marrow suppressive therapy involved in administration of the study treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02861300

Contacts
Contact: Jennifer Eads, MD 216-844-6031 jennifer.eads@uhhospitals.org

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Not yet recruiting
Cleveland, Ohio, United States, 44106
Contact: Jennifer Eads, MD    216-844-6031    jennifer.eads@uhhospitals.org   
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Alok Khorana, MD    216-626-2690    khorana@ccf.org   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Jennifer Eads, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02861300     History of Changes
Other Study ID Numbers: CASE1216 
Study First Received: August 5, 2016
Last Updated: August 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
CB-839
PIK3CA
capecitabine

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Rectal Diseases
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 25, 2016