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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

Phase 3
18 Years
Not Enrolling
Fallopian Tube Cancer, Fatigue, Neuropathy, Neurotoxicity, Ovarian Cancer, Pain, Primary Peritoneal Cavity Cancer

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Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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

- 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

- 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

- No poorly differentiated subtypes, including papillary serous, clear cell, or
other International Federation of Gynecology and Obstetrics (FIGO) grade 3

- 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


- 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


- 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)

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Outcome Measure:

Effect of ALC compared to placebo in preventing the chemotherapy-related peripheral neuropathy as measured with FACT/GOG-Ntx subscale

Safety Issue:


Principal Investigator

David M. Kushner, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Wisconsin, Madison



Study ID:




Start Date:

February 2012

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Fatigue
  • Neuropathy
  • Neurotoxicity
  • Ovarian Cancer
  • Pain
  • Primary Peritoneal Cavity Cancer
  • 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
  • Fatigue
  • Ovarian Neoplasms
  • Peripheral Nervous System Diseases
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neurotoxicity Syndromes
  • Demyelinating Diseases
  • Polyneuropathies
  • Nerve Compression Syndromes
  • Neurologic Manifestations
  • Neoplasms, Glandular and Epithelial