Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01492920
First received: December 14, 2011
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

RATIONALE: Acetyl-L-carnitine hydrochloride may prevent or lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether acetyl-L-carnitine hydrochloride is more effective compared to a placebo in preventing peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial studies how well acetyl-L-carnitine hydrochloride works compared to a placebo in preventing peripheral neuropathy in patients with recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer undergoing chemotherapy.


Condition Intervention Phase
Fallopian Tube Cancer
Fatigue
Neuropathy
Neurotoxicity
Ovarian Cancer
Pain
Primary Peritoneal Cavity Cancer
Dietary Supplement: acetyl-L-carnitine hydrochloride
Drug: carboplatin
Drug: cisplatin
Drug: paclitaxel
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Supportive Care
Official Title: A Randomized, Double-Blind, Placebo Controlled Phase III Trial Using ACETYL-L-Carnitine (ALC) (NSC# 747431) for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Effect of ALC compared to placebo in preventing the chemotherapy-related peripheral neuropathy as measured with FACT/GOG-Ntx subscale [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of ALC compared to placebo in preventing the chemotherapy-related fatigue as measured with FACT-Fatigue [ Designated as safety issue: No ]
  • Effect of ALC vs placebo on preventing the patient-reported sensory peripheral neuropathy, as measured by the FACT/GOG-Ntx_4 subscale [ Designated as safety issue: No ]
  • Effect of ALC on the quality of life, as measured by the FACT-O TOI [ Designated as safety issue: No ]

Enrollment: 0
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive acetyl-L-carnitine hydrochloride (ALC) orally (PO) twice daily (BID) on days 1-21 (during chemotherapy treatment).
Dietary Supplement: acetyl-L-carnitine hydrochloride
Given PO
Drug: carboplatin
Given systemically
Drug: cisplatin
Given systemically
Drug: paclitaxel
Given systemically
Placebo Comparator: Arm II
Patients receive placebo PO BID on days 1-21 (during chemotherapy treatment) (maximum of 8 courses).
Drug: carboplatin
Given systemically
Drug: cisplatin
Given systemically
Drug: paclitaxel
Given systemically
Other: placebo
Given PO

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the therapeutic efficacy of acetyl-L-carnitine hydrochloride (ALC) in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Secondary

  • Evaluate the effect of ALC on chemotherapy-induced fatigue based upon the Functional Assessment of Cancer Therapy (FACT)-Fatigue scale.
  • Evaluate the effect of ALC on sensory peripheral neuropathy as measured with the first 4 items of the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (FACT/GOG-Ntx_4 subscale).
  • Evaluate the effect of ALC on the health-related quality of life as measured by the FACT-Ovarian (O) trial outcome index (TOI).

OUTLINE: This is a multicenter study. Patients are stratified according to planned dosage of paclitaxel (< 150 mg/m^2 vs ≥ 150 mg/m^2), and age (< 60 years of age vs ≥ 6 years of age). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive acetyl-L-carnitine hydrochloride (ALC) orally (PO) twice daily (BID) on days 1-21 (during chemotherapy treatment).
  • Arm II: Patients receive placebo PO BID on days 1-21 (during chemotherapy treatment) (maximum of 8 courses).

In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients also complete questionnaires comprising the Functional Assessment of Cancer Therapy (FACT)-Fatigue scale, the FACT-Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx_4 subscale), and the FACT-Ovarian trial outcome index (FACT-O TOI) at baseline, prior to courses 3 and 5, within 4 weeks after completion of treatment, and then at 3 months after completion of treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent
  • Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner tumor, or adenocarcinoma not otherwise specified (N.O.S.)
  • All patients must have had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e., bevacizumab)

    • Front-line treatment may include maintenance therapy following complete clinical or pathological response; however, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease; patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy
    • Patients receiving hormonal therapy for biochemical or non-measurable recurrence disease are ELIGIBLE provided their recurrence is documented more than 6 months following the completion of primary cytotoxic chemotherapy; a minimum of 4 weeks must have expired since their last exposure to hormonal therapy

      • The complete response to front-line chemotherapy must have included a negative physical exam, normalization of CA125 if elevated at baseline, and negative radiographic assessment of disease, if obtained
      • Patients who have undergone reassessment laparotomy or laparoscopy following primary therapy are eligible for this study as long as they demonstrated a pathologic complete response based on the surgical assessment (i.e. all obtained specimens were histologically negative for disease)
  • Patients with a past history of primary endometrial cancer within the last five years are excluded unless all of the following conditions are met:

    • Stage not greater than IB
    • No more than superficial myometrial invasion, without vascular or lymphatic invasion
    • No poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
  • Patients must be expected to receive a minimum of 2 cycles of paclitaxel and a platinating agent for their recurrent disease; ;

    • Addition of other drugs such as bevacizumab is acceptable as long as these additional drugs are not typically associated with peripheral neuropathy
    • The initial, planned infusion duration of each dose of paclitaxel must be 3 hours or less

PATIENT CHARACTERISTICS:

  • Patients must start the study with a GOG performance status of 2 or less
  • Serum creatinine ≤ 2.5 mg/dL
  • Neuropathy (sensory and motor) less than or equal to the National Cancer Institute (NCI) CTCAE v4.0 grade 1
  • No patients with a history of seizure activity
  • No patients who are unable to swallow oral medications
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years
  • No patients of childbearing potential not practicing adequate contraception
  • No patients who are pregnant or nursing
  • No patients who are known to have diabetes

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients are excluded if their previous cancer treatment contraindicates this protocol therapy
  • No patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
  • No patients receiving concurrent immunotherapy or radiotherapy
  • No patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis
  • No patients who are currently receiving or have received warfarin or acenocoumarol within the past 7 days
  • No patients taking > 100 units of racemic vitamin E (or > 50 units of ααα-tocopherol) daily within 5 days of starting study therapy
  • No patients taking other medications (Rx, OTC, or dietary supplements) to prevent or treat neuropathy within 5 days of starting study treatment; such products include:

    • Gabapentin (Neurontin ®)
    • Pregabalin (Lyrica ®)
    • Duloxetine (Cymbalta ®)
    • Alpha-lipoic acid
    • Note that tricyclic antidepressants or selective serotonin/norepinephrine-selective reuptake inhibitors prescribed for the treatment of mood disorders are allowed
  • No patients with known allergies to ALC (acetyl-L-carnitine hydrochloride)
  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: NCT01492920

Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Study Chair: David M. Kushner, MD University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT01492920     History of Changes
Other Study ID Numbers: GOG-0257, CDR0000719317, NCI-2012-00090
Study First Received: December 14, 2011
Last Updated: September 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Gynecologic Oncology Group:
neurotoxicity
neuropathy
fatigue
pain
recurrent ovarian epithelial cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cavity cancer
ovarian serous cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian mucinous cystadenocarcinoma
ovarian clear cell cystadenocarcinoma
Brenner tumor

Additional relevant MeSH terms:
Fatigue
Ovarian Neoplasms
Peripheral Nervous System Diseases
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neurotoxicity Syndromes
Neoplasms, Glandular and Epithelial
Signs and Symptoms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neuromuscular Diseases
Nervous System Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Poisoning
Chemically-Induced Disorders
Neoplasms by Histologic Type
Acetylcarnitine
Carnitine

ClinicalTrials.gov processed this record on August 20, 2014